FAK signaling in human cancer as a target for therapeutics

Pharmacology and Therapeutics

Volumn 146, Issue , 2015, Pages 132-149

  Lee, Brian Y ^a   Timpson, Paul ^a,b   Horvath, Lisa G ^a,b,c,d,e   Daly, Roger J ^b,f  

^a GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

^c The Chris O Brien Lifehouse   (Australia)

^d ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^e UNIVERSITY OF SYDNEY   (Australia)

^f MONASH UNIVERSITY   (Australia)

Author keywords

Tumorigenesis Metastasis Tyrosine kinase Scaffold protein Tyrosine kinase inhibitor Cancer stem cells

Indexed keywords

2 [5 CHLORO 2 (2 METHOXY 4 MORPHOLINOANILINO) 4 PYRIMIDINYLAMINO] N METHYLBENZAMIDE; ACTIN; ANTINEOPLASTIC AGENT; BI 853520; DEFACTINIB; FOCAL ADHESION KINASE; FOCAL ADHESION KINASE INHIBITOR; GSK 2256098; MERLIN; PF 04554878; PF 562271; PF 573228; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; UNCLASSIFIED DRUG; VS 4718; Y 15; PROTEIN KINASE INHIBITOR;

ARTICLE; CANCER STEM CELL; CARCINOGENESIS; CELL CYCLE; CELL PROLIFERATION; CELL SURVIVAL; DRUG EFFICACY; EPITHELIAL MESENCHYMAL TRANSITION; FOCAL ADHESION; HUMAN; MESOTHELIOMA; METASTASIS; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR INVASION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; METABOLISM; NEOPLASMS;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL CYCLE; CELL SURVIVAL; FOCAL ADHESION PROTEIN-TYROSINE KINASES; HUMANS; NEOPLASM METASTASIS; NEOPLASMS; NEOPLASTIC STEM CELLS; PROTEIN KINASE INHIBITORS;

EID: 84921307176     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2014.10.001     Document Type: Article

References (276)

1. S. Abbi, H. Ueda, C. Zheng, L.A. Cooper, J. Zhao, and R. Christopher Regulation of focal adhesion kinase by a novel protein inhibitor FIP200 Mol Biol Cell 13 2002 3178 3191
2. H. Abedi, and I. Zachary Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells J Biol Chem 272 1997 15442 15451
3. M. Agochiya, V.G. Brunton, D.W. Owens, E.K. Parkinson, C. Paraskeva, and W.N. Keith Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells Oncogene 18 1999 5646 5653
4. T. Akagi, K. Murata, T. Shishido, and H. Hanafusa v-Crk activates the phosphoinositide 3-kinase/AKT pathway by utilizing focal adhesion kinase and H-Ras Mol Cell Biol 22 2002 7015 7023
5. A.N. Alexopoulou, C.M. Ho-Yen, V. Papalazarou, G. Elia, J.L. Jones, and K. Hodivala-Dilke Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer BMC Cancer 14 2014 237
6. M. Al-Hajj, M.S. Wicha, A. Benito-Hernandez, S.J. Morrison, and M.F. Clarke Prospective identification of tumorigenic breast cancer cells Proc Natl Acad Sci U S A 100 2003 3983 3988
7. B. Al-Lazikani, U. Banerji, and P. Workman Combinatorial drug therapy for cancer in the post-genomic era Nat Biotechnol 30 2012 679 692
8. E.A. Almeida, D. Ilic, Q. Han, C.R. Hauck, F. Jin, and H. Kawakatsu Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase J Cell Biol 149 2000 741 754
9. G.H. Ashton, J.P. Morton, K. Myant, T.J. Phesse, R.A. Ridgway, and V. Marsh Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling Dev Cell 19 2010 259 269
10. E. Avizienyte, and M.C. Frame Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal transition Curr Opin Cell Biol 17 2005 542 547
11. E. Avizienyte, A.W. Wyke, R.J. Jones, G.W. McLean, M.A. Westhoff, and V.G. Brunton Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling Nat Cell Biol 4 2002 632 638
12. C.M. Bagi, J. Christensen, D.P. Cohen, W.G. Roberts, D. Wilkie, and T. Swanson Sunitinib and PF-562,271 (FAK/Pyk2 inhibitor) effectively block growth and recovery of human hepatocellular carcinoma in a rat xenograft model Cancer Biol Ther 8 2009 856 865
13. C.M. Bagi, G.W. Roberts, and C.J. Andresen Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases Cancer 112 2008 2313 2321
14. S. Barbero, A. Mielgo, V. Torres, T. Teitz, D.J. Shields, and D. Mikolon Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis Cancer Res 69 2009 3755 3763
15. S. Basu, N.F. Totty, M.S. Irwin, M. Sudol, and J. Downward Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis Mol Cell 11 2003 11 23
16. E.A. Beierle, A. Trujillo, A. Nagaram, V.M. Golubovskaya, W.G. Cance, and E.V. Kurenova TAE226 inhibits human neuroblastoma cell survival Cancer Investig 26 2008 145 151
17. R.B. Birge, J.E. Fajardo, C. Reichman, S.E. Shoelson, Z. Songyang, and L.C. Cantley Identification and characterization of a high-affinity interaction between v-Crk and tyrosine-phosphorylated paxillin in CT10-transformed fibroblasts Mol Cell Biol 13 1993 4648 4656
18. J. Bottsford-Miller, A. Sanguino, D. Thanapprapasr, C.V. Pecot, R.L. Stone, and K. Auger Enhancing anti-angiogenic therapy by blocking focal adhesion kinase Cancer Res 71 Suppl. 1 2011
19. V. Bouchard, M.J. Demers, S. Thibodeau, V. Laquerre, N. Fujita, and T. Tsuruo Fak/Src signaling in human intestinal epithelial cell survival and anoikis: differentiation state-specific uncoupling with the PI3-K/Akt-1 and MEK/Erk pathways J Cell Physiol 212 2007 717 728
20. K. Brami-Cherrier, N. Gervasi, D. Arsenieva, K. Walkiewicz, M.C. Boutterin, and A. Ortega FAK dimerization controls its kinase-dependent functions at focal adhesions EMBO J 33 2014 356 370
21. E. Brugnera, L. Haney, C. Grimsley, M. Lu, S.F. Walk, and A.C. Tosello-Trampont Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex Nat Cell Biol 4 2002 574 582
22. A. Brunet, A. Bonni, M.J. Zigmond, M.Z. Lin, P. Juo, and L.S. Hu Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor Cell 96 1999 857 868
23. V.G. Brunton, B.W. Ozanne, C. Paraskeva, and M.C. Frame A role for epidermal growth factor receptor, c-Src and focal adhesion kinase in an in vitro model for the progression of colon cancer Oncogene 14 1997 283 293
24. K. Burridge, C.E. Turner, and L.H. Romer Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly J Cell Biol 119 1992 893 903
25. X. Cai, D. Lietha, D.F. Ceccarelli, A.V. Karginov, Z. Rajfur, and K. Jacobson Spatial and temporal regulation of focal adhesion kinase activity in living cells Mol Cell Biol 28 2008 201 214
26. M.B. Calalb, T.R. Polte, and S.K. Hanks Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases Mol Cell Biol 15 1995 954 963
27. W.G. Cance, J.E. Harris, M.V. Iacocca, E. Roche, X. Yang, and J. Chang Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes Clin Cancer Res 6 2000 2417 2423
28. W.G. Cance, E. Kurenova, T. Marlowe, and V. Golubovskaya Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics Sci Signal 6 2013 pe10
29. M. Canel, P. Secades, J.P. Rodrigo, R. Cabanillas, A. Herrero, and C. Suarez Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number Clin Cancer Res 12 2006 3272 3279
30. M. Canel, A. Serrels, D. Miller, P. Timpson, B. Serrels, and M.C. Frame Quantitative in vivo imaging of the effects of inhibiting integrin signaling via Src and FAK on cancer cell movement: effects on E-cadherin dynamics Cancer Res 70 2010 9413 9422
31. M.H. Cardone, N. Roy, H.R. Stennicke, G.S. Salvesen, T.F. Franke, and E. Stanbridge Regulation of cell death protease caspase-9 by phosphorylation Science 282 1998 1318 1321
32. S. Carelli, G. Zadra, V. Vaira, M. Falleni, L. Bottiglieri, and M. Nosotti Up-regulation of focal adhesion kinase in non-small cell lung cancer Lung Cancer 53 2006 263 271
33. N.O. Carragher, M.A. Westhoff, V.J. Fincham, M.D. Schaller, and M.C. Frame A novel role for FAK as a protease-targeting adaptor protein: regulation by p42 ERK and Src Curr Biol 13 2003 1442 1450
34. K.T. Chan, D.A. Bennin, and A. Huttenlocher Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK) J Biol Chem 285 2010 11418 11426
35. P.C. Chan, J.F. Lai, C.H. Cheng, M.J. Tang, C.C. Chiu, and H.C. Chen Suppression of ultraviolet irradiation-induced apoptosis by overexpression of focal adhesion kinase in Madin-Darby canine kidney cells J Biol Chem 274 1999 26901 26906
36. N.A. Chatzizacharias, G.P. Kouraklis, and S.E. Theocharis Clinical significance of FAK expression in human neoplasia Histol Histopathol 23 2008 629 650
37. H.C. Chen, P.A. Appeddu, H. Isoda, and J.L. Guan Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase J Biol Chem 271 1996 26329 26334
38. H.C. Chen, P.A. Appeddu, J.T. Parsons, J.D. Hildebrand, M.D. Schaller, and J.L. Guan Interaction of focal adhesion kinase with cytoskeletal protein talin J Biol Chem 270 1995 16995 16999
39. T.H. Chen, P.C. Chan, C.L. Chen, and H.C. Chen Phosphorylation of focal adhesion kinase on tyrosine 194 by Met leads to its activation through relief of autoinhibition Oncogene 30 2011 153 166
40. H.C. Chen, P.C. Chan, M.J. Tang, C.H. Cheng, and T.J. Chang Tyrosine phosphorylation of focal adhesion kinase stimulated by hepatocyte growth factor leads to mitogen-activated protein kinase activation J Biol Chem 273 1998 25777 25782
41. S.Y. Chen, and H.C. Chen Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion Mol Cell Biol 26 2006 5155 5167
42. H.C. Chen, and J.L. Guan Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase Proc Natl Acad Sci U S A 91 1994 10148 10152
43. S. Chen, N. Johnson, K.R. Auger, Y. Xiao, H. Ying, and J. Marszalek Characterization of a selective focal adhesion kinase (FAK) inhibitor in a panel of glioblastoma cell lines identify rational drug-drug combination strategies Cancer Res 72 2012
44. R. Chen, O. Kim, M. Li, X. Xiong, J.L. Guan, and H.J. Kung Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain Nat Cell Biol 3 2001 439 444
45. X.L. Chen, J.O. Nam, C. Jean, C. Lawson, C.T. Walsh, and E. Goka VEGF-induced vascular permeability is mediated by FAK Dev Cell 22 2012 146 157
46. Y. Chen, V. Rodrik, and D.A. Foster Alternative phospholipase D/mTOR survival signal in human breast cancer cells Oncogene 24 2005 672 679
47. Y.Y. Chen, Z.X. Wang, P.A. Chang, J.J. Li, F. Pan, and L. Yang Knockdown of focal adhesion kinase reverses colon carcinoma multicellular resistance Cancer Sci 100 2009 1708 1713
48. Y. Chen, Z. Wang, P. Chang, L. Xiang, F. Pan, and J. Li The effect of focal adhesion kinase gene silencing on 5-fluorouracil chemosensitivity involves an Akt/NF-kappaB signaling pathway in colorectal carcinomas Int J Cancer 127 2010 195 206
49. D. Chodniewicz, and R.L. Klemke Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold Biochim Biophys Acta 1692 2004 63 76
50. C.H. Choi, B.A. Webb, M.S. Chimenti, M.P. Jacobson, and D.L. Barber pH sensing by FAK-His58 regulates focal adhesion remodeling J Cell Biol 202 2013 849 859
51. C. Cicchini, I. Laudadio, F. Citarella, M. Corazzari, C. Steindler, and A. Conigliaro TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling Exp Cell Res 314 2008 143 152
52. J.R. Conway, N.O. Carragher, and P. Timpson Developments in preclinical cancer imaging: innovating the discovery of therapeutics Nat Rev Cancer 14 2014 314 328
53. N. Cordes, S. Frick, T.B. Brunner, C. Pilarsky, R. Grutzmann, and B. Sipos Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1 Oncogene 26 2007 6851 6862
54. B.D. Crompton, A.L. Carlton, A.R. Thorner, A.L. Christie, J. Du, and M.L. Calicchio High-throughput tyrosine kinase activity profiling identifies FAK as a candidate therapeutic target in Ewing sarcoma Cancer Res 73 2013 2873 2883
55. S.R. Datta, H. Dudek, X. Tao, S. Masters, H. Fu, and Y. Gotoh Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery Cell 91 1997 231 241
56. Q. Ding, J.R. Grammer, M.A. Nelson, J.L. Guan, J.E. Stewart Jr., and C.L. Gladson p27Kip1 and cyclin D1 are necessary for focal adhesion kinase regulation of cell cycle progression in glioblastoma cells propagated in vitro and in vivo in the scid mouse brain J Biol Chem 280 2005 6802 6815
57. B.J. Druker, C.L. Sawyers, H. Kantarjian, D.J. Resta, S.F. Reese, and J.M. Ford Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome N Engl J Med 344 2001 1038 1042
58. M.S. Duxbury, H. Ito, E. Benoit, M.J. Zinner, S.W. Ashley, and E.E. Whang RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity Biochem Biophys Res Commun 311 2003 786 792
59. M.S. Duxbury, H. Ito, M.J. Zinner, S.W. Ashley, and E.E. Whang Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells Surgery 135 2004 555 562
60. A.L. Edinger, and C.B. Thompson Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake Mol Biol Cell 13 2002 2276 2288
61. B.P. Eliceiri, X.S. Puente, J.D. Hood, D.G. Stupack, D.D. Schlaepfer, and X.Z. Huang Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling J Cell Biol 157 2002 149 160
62. A. Eramo, F. Lotti, G. Sette, E. Pilozzi, M. Biffoni, and A. Di Virgilio Identification and expansion of the tumorigenic lung cancer stem cell population Cell Death Differ 15 2008 504 514
63. H. Fan, X. Zhao, S. Sun, M. Luo, and J.L. Guan Function of focal adhesion kinase scaffolding to mediate endophilin A2 phosphorylation promotes epithelial-mesenchymal transition and mammary cancer stem cell activities in vivo J Biol Chem 288 2013 3322 3333
64. X.Q. Fang, X.F. Liu, L. Yao, C.Q. Chen, Z.D. Gu, and P.H. Ni Somatic mutational analysis of FAK in breast cancer: a novel gain-of-function mutation due to deletion of exon 33 Biochem Biophys Res Commun 443 2014 363 369
65. X. Fang, X. Liu, L. Yao, C. Chen, J. Lin, and P. Ni New insights into FAK phosphorylation based on a FAT domain-defective mutation PLoS ONE 9 2014 e107134
66. M.C. Frame, H. Patel, B. Serrels, D. Lietha, and M.J. Eck The FERM domain: organizing the structure and function of FAK Nat Rev Mol Cell Biol 11 2010 802 814
67. S.J. Franco, and A. Huttenlocher Regulating cell migration: calpains make the cut J Cell Sci 118 2005 3829 3838
68. P. Friedl, and K. Wolf Tumour-cell invasion and migration: diversity and escape mechanisms Nat Rev Cancer 3 2003 362 374
69. S.M. Frisch, and E. Ruoslahti Integrins and anoikis Curr Opin Cell Biol 9 1997 701 706
70. S.M. Frisch, K. Vuori, E. Ruoslahti, and P.Y. Chan-Hui Control of adhesion-dependent cell survival by focal adhesion kinase J Cell Biol 134 1996 793 799
71. T. Fujii, K. Koshikawa, S. Nomoto, O. Okochi, T. Kaneko, and S. Inoue Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be served as an independent prognostic factor J Hepatol 41 2004 104 111
72. K. Furuyama, R. Doi, T. Mori, E. Toyoda, D. Ito, and K. Kami Clinical significance of focal adhesion kinase in resectable pancreatic cancer World J Surg 30 2006 219 226
73. V. Gabarra-Niecko, M.D. Schaller, and J.M. Dunty FAK regulates biological processes important for the pathogenesis of cancer Cancer Metastasis Rev 22 2003 359 374
74. B. Gabriel, A. zur Hausen, E. Stickeler, C. Dietz, G. Gitsch, and D.C. Fischer Weak expression of focal adhesion kinase (pp125FAK) in patients with cervical cancer is associated with poor disease outcome Clin Cancer Res 12 2006 2476 2483
75. C.A. Garces, E.V. Kurenova, V.M. Golubovskaya, and W.G. Cance Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells Cancer Res 66 2006 1446 1454
76. S. Garcia, J.P. Dales, E. Charafe-Jauffret, S. Carpentier-Meunier, L. Andrac-Meyer, and J. Jacquemier Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast carcinomas correlates with shorter survival and neoangiogenesis Int J Oncol 31 2007 49 58
77. R.E. Gates, L.E. King Jr., S.K. Hanks, and L.B. Nanney Potential role for focal adhesion kinase in migrating and proliferating keratinocytes near epidermal wounds and in culture Cell Growth Differ 5 1994 891 899
78. F.G. Giancotti, and E. Ruoslahti Integrin signaling Science 285 1999 1028 1032
79. A.P. Gilmore, A.D. Metcalfe, L.H. Romer, and C.H. Streuli Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization J Cell Biol 149 2000 431 446
80. A.P. Gilmore, and L.H. Romer Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation Mol Biol Cell 7 1996 1209 1224
81. V.M. Golubovskaya Targeting FAK in human cancer: from finding to first clinical trials Front Biosci (Landmark Ed) 19 2014 687 706
82. V.M. Golubovskaya, and W.G. Cance Focal adhesion kinase and p53 signaling in cancer cells Int Rev Cytol 263 2007 103 153
83. V.M. Golubovskaya, K. Conway-Dorsey, S.N. Edmiston, C.K. Tse, A.A. Lark, and C.A. Livasy FAK overexpression and p53 mutations are highly correlated in human breast cancer Int J Cancer 125 2009 1735 1738
84. V.M. Golubovskaya, R. Finch, and W.G. Cance Direct interaction of the N-terminal domain of focal adhesion kinase with the N-terminal transactivation domain of p53 J Biol Chem 280 2005 25008 25021
85. V.M. Golubovskaya, R. Finch, F. Kweh, N.A. Massoll, M. Campbell-Thompson, and M.R. Wallace p53 regulates FAK expression in human tumor cells Mol Carcinog 47 2008 373 382
86. V.M. Golubovskaya, B. Ho, M. Zheng, A. Magis, D. Ostrov, and C. Morrison Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth BMC Cancer 13 2013 342
87. V.M. Golubovskaya, G. Huang, B. Ho, M. Yemma, C.D. Morrison, and J. Lee Pharmacologic blockade of FAK autophosphorylation decreases human glioblastoma tumor growth and synergizes with temozolomide Mol Cancer Ther 12 2013 162 172
88. V. Golubovskaya, A. Kaur, and W. Cance Cloning and characterization of the promoter region of human focal adhesion kinase gene: nuclear factor kappa B and p53 binding sites Biochim Biophys Acta 1678 2004 111 125
89. V.M. Golubovskaya, N.L. Palma, M. Zheng, B. Ho, A. Magis, and D. Ostrov A small-molecule inhibitor, 5′-O-tritylthymidine, targets FAK and Mdm-2 interaction, and blocks breast and colon tumorigenesis in vivo Anticancer Agents Med Chem 13 2013 532 545
90. G.M. Goni, C. Epifano, J. Boskovic, M. Camacho-Artacho, J. Zhou, and A. Bronowska Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes Proc Natl Acad Sci U S A 111 2014 E3177 E3186
91. K. Graham FAK deletion promotes p53-mediated induction of p21, DNA-damage responses and ratio-resistance in advanced squamous cancer cells PLoS ONE 6 2011 1 15
92. J.L. Guan, and D. Shalloway Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation Nature 358 1992 690 692
93. S.L. Gupton, and C.M. Waterman-Storer Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration Cell 125 2006 1361 1374
94. J. Halder, C.N. Landen Jr., S.K. Lutgendorf, Y. Li, N.B. Jennings, and D. Fan Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells Clin Cancer Res 11 2005 8829 8836
95. J. Halder, Y.G. Lin, W.M. Merritt, W.A. Spannuth, A.M. Nick, and T. Honda Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma Cancer Res 67 2007 10976 10983
96. S.K. Hanks, L. Ryzhova, N.Y. Shin, and J. Brabek Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility Front Biosci 8 2003 d982 d996
97. C.R. Hauck, D.A. Hsia, D. Ilic, and D.D. Schlaepfer v-Src SH3-enhanced interaction with focal adhesion kinase at beta 1 integrin-containing invadopodia promotes cell invasion J Biol Chem 277 2002 12487 12490
98. C.R. Hauck, D.A. Hsia, X.S. Puente, D.A. Cheresh, and D.D. Schlaepfer FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth EMBO J 21 2002 6289 6302
99. C.R. Hauck, D.J. Sieg, D.A. Hsia, J.C. Loftus, W.A. Gaarde, and B.P. Monia Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells Cancer Res 61 2001 7079 7090
100. M. Heffler, V.M. Golubovskaya, K.M. Dunn, and W. Cance Focal adhesion kinase autophosphorylation inhibition decreases colon cancer cell growth and enhances the efficacy of chemotherapy Cancer Biol Ther 14 2013 761 772
101. A.R. Hess, L.M. Postovit, N.V. Margaryan, E.A. Seftor, G.B. Schneider, and R.E. Seftor Focal adhesion kinase promotes the aggressive melanoma phenotype Cancer Res 65 2005 9851 9860
102. U.A. Hirt, J. Braunger, M. Schleicher, U. Weyer-Czernilofsky, P. Garin-Chesa, and B. Bister BI 853520, a potent and highly selective inhibitor of protein tyrosine kinase 2 (focal adhesion kinase), shows efficacy in multiple xenograft models of human cancer Mol Cancer Ther 10 11 Suppl. 2011 (Abstr A249)
103. F. Hochgrafe, L. Zhang, S.A. O'Toole, B.C. Browne, M. Pinese, and A. Porta Cubas Tyrosine phosphorylation profiling reveals the signaling network characteristics of basal breast cancer cells Cancer Res 70 2010 9391 9401
104. S.N. Hochwald, C. Nyberg, M. Zheng, D. Zheng, C. Wood, and N.A. Massoll A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer Cell Cycle 8 2009 2435 2443
105. J.C. Horowitz, D.S. Rogers, V. Sharma, R. Vittal, E.S. White, and Z. Cui Combinatorial activation of FAK and AKT by transforming growth factor-beta1 confers an anoikis-resistant phenotype to myofibroblasts Cell Signal 19 2007 761 771
106. D.A. Hsia, S.K. Mitra, C.R. Hauck, D.N. Streblow, J.A. Nelson, and D. Ilic Differential regulation of cell motility and invasion by FAK J Cell Biol 160 2003 753 767
107. N.Y. Hsu, C.Y. Chen, C.P. Hsu, T.Y. Lin, M.C. Chou, and S.H. Chiou Prognostic significance of expression of nm23-H1 and focal adhesion kinase in non-small cell lung cancer Oncol Rep 18 2007 81 85
108. D. Huang, M. Khoe, M. Befekadu, S. Chung, Y. Takata, and D. Ilic Focal adhesion kinase mediates cell survival via NF-kappaB and ERK signaling pathways Am J Physiol Cell Physiol 292 2007 C1339 C1352
109. Y.T. Huang, L.T. Lee, P.P. Lee, Y.S. Lin, and M.T. Lee Targeting of focal adhesion kinase by flavonoids and small-interfering RNAs reduces tumor cell migration ability Anticancer Res 25 2005 2017 2025
110. E.M. Hurt, K. Chan, M.A. Serrat, S.B. Thomas, T.D. Veenstra, and W.L. Farrar Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation Stem Cells 28 2010 390 398
111. D. Ilic, E.A. Almeida, D.D. Schlaepfer, P. Dazin, S. Aizawa, and C.H. Damsky Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis J Cell Biol 143 1998 547 560
112. D. Ilic, Y. Furuta, S. Kanazawa, N. Takeda, K. Sobue, and N. Nakatsuji Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice Nature 377 1995 539 544
113. D. Ilic, B. Kovacic, S. McDonagh, F. Jin, C. Baumbusch, and D.G. Gardner Focal adhesion kinase is required for blood vessel morphogenesis Circ Res 92 2003 300 307
114. J.R. Infante, D.R. Camidge, L.R. Mileshkin, E.X. Chen, R.J. Hicks, and D. Rischin Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors J Clin Oncol 30 2012 1527 1533
115. M.P. Iwanicki, T. Vomastek, R.W. Tilghman, K.H. Martin, J. Banerjee, and P.B. Wedegaertner FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts J Cell Sci 121 2008 895 905
116. C. Jean, X.L. Chen, J.O. Nam, I. Tancioni, S. Uryu, and C. Lawson Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function J Cell Biol 204 2014 247 263
117. SF Jones, G. Shapiro, J.C. Bendell, E.X. Chen, P. Bedard, and J.M. Cleary Phase I study of PF-04554878, a second-generation focal adhesion kinase (FAK) inhibitor, in patients with advanced solid tumors J Clin Oncol 29 2011 (Suppl.; abstr 3002)
118. G. Jones, J. Machado Jr., and A. Merlo Loss of focal adhesion kinase (FAK) inhibits epidermal growth factor receptor-dependent migration and induces aggregation of nh(2)-terminal FAK in the nuclei of apoptotic glioblastoma cells Cancer Res 61 2001 4978 4981
119. G. Jones, J. Machado Jr., M. Tolnay, and A. Merlo PTEN-independent induction of caspase-mediated cell death and reduced invasion by the focal adhesion targeting domain (FAT) in human astrocytic brain tumors which highly express focal adhesion kinase (FAK) Cancer Res 61 2001 5688 5691
120. I. Joshi, T. Yoshida, N. Jena, X. Qi, J. Zhang, and R.A. Van Etten Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia Nat Immunol 15 2014 294 304
121. P.L. Judson, X. He, W.G. Cance, and L. Van Le Overexpression of focal adhesion kinase, a protein tyrosine kinase, in ovarian carcinoma Cancer 86 1999 1551 1556
122. R. Kalluri, and R.A. Weinberg The basics of epithelial-mesenchymal transition J Clin Invest 119 2009 1420 1428
123. P. Kamarajan, and Y.L. Kapila An altered fibronectin matrix induces anoikis of human squamous cell carcinoma cells by suppressing integrin alpha v levels and phosphorylation of FAK and ERK Apoptosis 12 2007 2221 2231
124. T. Kaneda, Y. Sonoda, K. Ando, T. Suzuki, Y. Sasaki, and T. Oshio Mutation of Y925F in focal adhesion kinase (FAK) suppresses melanoma cell proliferation and metastasis Cancer Lett 270 2008 354 361
125. Y. Kang, W. Hu, C. Ivan, H.J. Dalton, T. Miyake, and C.V. Pecot Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer J Natl Cancer Inst 105 2013 1485 1495
126. S.B. Kanner, A.B. Reynolds, R.R. Vines, and J.T. Parsons Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases Proc Natl Acad Sci U S A 87 1990 3328 3332
127. S. Kim, H.Y. Kang, E.H. Nam, M.S. Choi, X.F. Zhao, and C.S. Hong TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways Carcinogenesis 31 2010 597 606
128. S.J. Kim, J.W. Park, J.S. Yoon, J.O. Mok, Y.J. Kim, and H.K. Park Increased expression of focal adhesion kinase in thyroid cancer: immunohistochemical study J Korean Med Sci 19 2004 710 715
129. V. Kostourou, T. Lechertier, L.E. Reynolds, D.M. Lees, M. Baker, and D.T. Jones FAK-heterozygous mice display enhanced tumour angiogenesis Nat Commun 4 2013 2020
130. E.V. Kurenova, D.L. Hunt, D. He, A.T. Magis, D.A. Ostrov, and W.G. Cance Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo J Med Chem 52 2009 4716 4724
131. E. Kurenova, L.H. Xu, X. Yang, A.S. Baldwin Jr., R.J. Craven, and S.K. Hanks Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein Mol Cell Biol 24 2004 4361 4371
132. N. Kurio, T. Shimo, T. Fukazawa, T. Okui, N.M. Hassan, and T. Honami Anti-tumor effect of a novel FAK inhibitor TAE226 against human oral squamous cell carcinoma Oral Oncol 48 2012 1159 1170
133. N. Kurio, T. Shimo, T. Fukazawa, M. Takaoka, T. Okui, and N.M. Hassan Anti-tumor effect in human breast cancer by TAE226, a dual inhibitor for FAK and IGF-IR in vitro and in vivo Exp Cell Res 317 2011 1134 1146
134. H. Lahlou, V. Sanguin-Gendreau, M.C. Frame, and W.J. Muller Focal adhesion kinase contributes to proliferative potential of ErbB2 mammary tumour cells but is dispensable for ErbB2 mammary tumour induction in vivo Breast Cancer Res 14 2012 R36
135. H. Lahlou, V. Sanguin-Gendreau, D. Zuo, R.D. Cardiff, G.W. McLean, and M.C. Frame Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression Proc Natl Acad Sci U S A 104 2007 20302 20307
136. A.L. Lark, C.A. Livasy, L. Dressler, D.T. Moore, R.C. Millikan, and J. Geradts High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype Mod Pathol 18 2005 1289 1294
137. D.A. Lauffenburger, and A.F. Horwitz Cell migration: a physically integrated molecular process Cell 84 1996 359 369
138. C. Lawson, S.T. Lim, S. Uryu, X.L. Chen, D.A. Calderwood, and D.D. Schlaepfer FAK promotes recruitment of talin to nascent adhesions to control cell motility J Cell Biol 196 2012 223 232
139. B.Y. Lee, F. Hochgrafe, H.M. Lin, L. Castillo, J. Wu, and M.J. Raftery Phosphoproteomic profiling identifies focal adhesion kinase as a mediator of docetaxel resistance in castrate-resistant prostate cancer Mol Cancer Ther 13 2014 190 201
140. S. Lee, J. Qiao, P. Paul, K.L. O'Connor, M.B. Evers, and D.H. Chung FAK is a critical regulator of neuroblastoma liver metastasis Oncotarget 3 2012 1576 1587
141. K.R. Levental, H. Yu, L. Kass, J.N. Lakins, M. Egeblad, and J.T. Erler Matrix crosslinking forces tumor progression by enhancing integrin signaling Cell 139 2009 891 906
142. D. Lietha, X. Cai, D.F. Ceccarelli, Y. Li, M.D. Schaller, and M.J. Eck Structural basis for the autoinhibition of focal adhesion kinase Cell 129 2007 1177 1187
143. S.T. Lim, X.L. Chen, Y. Lim, D.A. Hanson, T.T. Vo, and K. Howerton Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation Mol Cell 29 2008 9 22
144. Y. Lim, S.T. Lim, A. Tomar, M. Gardel, J.A. Bernard-Trifilo, and X.L. Chen PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility J Cell Biol 180 2008 187 203
145. S.T. Lim, D. Mikolon, D.G. Stupack, and D.D. Schlaepfer FERM control of FAK function: implications for cancer therapy Cell Cycle 7 2008 2306 2314
146. W. Liu, D.A. Bloom, W.G. Cance, E.V. Kurenova, V.M. Golubovskaya, and S.N. Hochwald FAK and IGF-IR interact to provide survival signals in human pancreatic adenocarcinoma cells Carcinogenesis 29 2008 1096 1107
147. T.J. Liu, T. LaFortune, T. Honda, O. Ohmori, S. Hatakeyama, and T. Meyer Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo Mol Cancer Ther 6 2007 1357 1367
148. Y. Liu, J.C. Loijens, K.H. Martin, A.V. Karginov, and J.T. Parsons The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly Mol Biol Cell 13 2002 2147 2156
149. C.A. Livasy, D. Moore, W.G. Cance, and R.A. Lininger Focal adhesion kinase overexpression in endometrial neoplasia Appl Immunohistochem Mol Morphol 12 2004 342 345
150. M. Lobo, and I. Zachary Nuclear localization and apoptotic regulation of an amino-terminal domain focal adhesion kinase fragment in endothelial cells Biochem Biophys Res Commun 276 2000 1068 1074
151. W. Long, P. Yi, L. Amazit, H.L. LaMarca, F. Ashcroft, and R. Kumar SRC-3Delta4 mediates the interaction of EGFR with FAK to promote cell migration Mol Cell 37 2010 321 332
152. M. Luo, H. Fan, T. Nagy, H. Wei, C. Wang, and S. Liu Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells Cancer Res 69 2009 466 474
153. M. Luo, X. Zhao, S. Chen, S. Liu, M.S. Wicha, and J.L. Guan Distinct FAK activities determine progenitor and mammary stem cell characteristics Cancer Res 73 2013 5591 5602
154. L.M. Machesky, and R.H. Insall Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex Curr Biol 8 1998 1347 1356
155. R. Madan, M.B. Smolkin, R. Cocker, R. Fayyad, and M.H. Oktay Focal adhesion proteins as markers of malignant transformation and prognostic indicators in breast carcinoma Hum Pathol 37 2006 9 15
156. G.W. McLean, N.O. Carragher, E. Avizienyte, J. Evans, V.G. Brunton, and M.C. Frame The role of focal-adhesion kinase in cancer - a new therapeutic opportunity Nat Rev Cancer 5 2005 505 515
157. G.W. McLean, N.H. Komiyama, B. Serrels, H. Asano, L. Reynolds, and F. Conti Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression Genes Dev 18 2004 2998 3003
158. X.N. Meng, Y. Jin, Y. Yu, J. Bai, G.Y. Liu, and J. Zhu Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion Br J Cancer 101 2009 327 334
159. R. Menon, M. Deng, K. Ruenauver, A. Queisser, M. Peifer, and A. Offermann Somatic copy number alterations by whole-exome sequencing implicates YWHAZ and PTK2 in castration-resistant prostate cancer J Pathol 231 2013 505 516
160. H. Miao, E. Burnett, M. Kinch, E. Simon, and B. Wang Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation Nat Cell Biol 2 2000 62 69
161. N.L. Miller, C. Lawson, E.G. Kleinschmidt, I. Tancioni, S. Uryu, and D.D. Schlaepfer A non-canonical role for Rgnef in promoting integrin-stimulated focal adhesion kinase activation J Cell Sci 126 2013 5074 5085
162. S.K. Mitra, D.A. Hanson, and D.D. Schlaepfer Focal adhesion kinase: in command and control of cell motility Nat Rev Mol Cell Biol 6 2005 56 68
163. S.K. Mitra, D. Mikolon, J.E. Molina, D.A. Hsia, D.A. Hanson, and A. Chi Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors Oncogene 25 2006 5969 5984
164. S.K. Mitra, and D.D. Schlaepfer Integrin-regulated FAK-Src signaling in normal and cancer cells Curr Opin Cell Biol 18 2006 516 523
165. T. Miyazaki, H. Kato, M. Nakajima, M. Sohda, Y. Fukai, and N. Masuda FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma Br J Cancer 89 2003 140 145
166. J.P. Morton, P. Timpson, S.A. Karim, R.A. Ridgway, D. Athineos, and B. Doyle Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer Proc Natl Acad Sci U S A 107 2010 246 251
167. C.D. Nobes, and A. Hall Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia Cell 81 1995 53 62
168. C.D. Nobes, and A. Hall Rho GTPases control polarity, protrusion, and adhesion during cell movement J Cell Biol 144 1999 1235 1244
169. H. Okamoto, K. Yasui, C. Zhao, S. Arii, and J. Inazawa PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated with large hepatocellular carcinomas Hepatology 38 2003 1242 1249
170. M.H. Oktay, K. Oktay, D. Hamele-Bena, A. Buyuk, and L.G. Koss Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas Hum Pathol 34 2003 240 245
171. M. Oktay, K.K. Wary, M. Dans, R.B. Birge, and F.G. Giancotti Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH2-terminal kinase and progression through the G1 phase of the cell cycle J Cell Biol 145 1999 1461 1469
172. L.V. Owens, L. Xu, R.J. Craven, G.A. Dent, T.M. Weiner, and L. Kornberg Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors Cancer Res 55 1995 2752 2755
173. C.A. Parent, and P.N. Devreotes A cell's sense of direction Science 284 1999 765 770
174. J.H. Park, B.L. Lee, J. Yoon, J. Kim, M.A. Kim, and H.K. Yang Focal adhesion kinase (FAK) gene amplification and its clinical implications in gastric cancer Hum Pathol 41 2010 1664 1673
175. J.T. Parsons Focal adhesion kinase: the first ten years J Cell Sci 116 2003 1409 1416
176. D.M. Pirone, W.F. Liu, S.A. Ruiz, L. Gao, S. Raghavan, and C.A. Lemmon An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling J Cell Biol 174 2006 277 288
177. M.P. Playford, and M.D. Schaller The interplay between Src and integrins in normal and tumor biology Oncogene 23 2004 7928 7946
178. T.R. Polte, and S.K. Hanks Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas Proc Natl Acad Sci U S A 92 1995 10678 10682
179. T.R. Polte, A.J. Naftilan, and S.K. Hanks Focal adhesion kinase is abundant in developing blood vessels and elevation of its phosphotyrosine content in vascular smooth muscle cells is a rapid response to angiotensin II J Cell Biochem 55 1994 106 119
180. P. Poullet, A. Gautreau, G. Kadare, J.A. Girault, D. Louvard, and M. Arpin Ezrin interacts with focal adhesion kinase and induces its activation independently of cell-matrix adhesion J Biol Chem 276 2001 37686 37691
181. P.P. Provenzano, D.R. Inman, K.W. Eliceiri, H.E. Beggs, and P.J. Keely Mammary epithelial-specific disruption of focal adhesion kinase retards tumor formation and metastasis in a transgenic mouse model of human breast cancer Am J Pathol 173 2008 1551 1565
182. Y. Pylayeva, K.M. Gillen, W. Gerald, H.E. Beggs, L.F. Reichardt, and F.G. Giancotti Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling J Clin Invest 119 2009 252 266
183. P.A. Randazzo, J. Andrade, K. Miura, M.T. Brown, Y.Q. Long, and S. Stauffer The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton Proc Natl Acad Sci U S A 97 2000 4011 4016
184. S. Rankin, and E. Rozengurt Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and paxillin tyrosine phosphorylation in Swiss 3 T3 cells. Bell-shaped dose response and cross-talk with bombesin J Biol Chem 269 1994 704 710
185. P.J. Reddig, and R.L. Juliano Clinging to life: cell to matrix adhesion and cell survival Cancer Metastasis Rev 24 2005 425 439
186. X.R. Ren, Q.S. Du, Y.Z. Huang, S.Z. Ao, L. Mei, and W.C. Xiong Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein J Cell Biol 152 2001 971 984
187. A. Richardson, R.K. Malik, J.D. Hildebrand, and J.T. Parsons Inhibition of cell spreading by expression of the C-terminal domain of focal adhesion kinase (FAK) is rescued by coexpression of Src or catalytically inactive FAK: a role for paxillin tyrosine phosphorylation Mol Cell Biol 17 1997 6906 6914
188. R.A. Ridgway, B. Serrels, S. Mason, A. Kinnaird, M. Muir, and H. Patel Focal adhesion kinase is required for beta-catenin-induced mobilization of epidermal stem cells Carcinogenesis 33 2012 2369 2376
189. A.J. Ridley, M.A. Schwartz, K. Burridge, R.A. Firtel, M.H. Ginsberg, and G. Borisy Cell migration: integrating signals from front to back Science 302 2003 1704 1709
190. W.G. Roberts, E. Ung, P. Whalen, B. Cooper, C. Hulford, and C. Autry Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271 Cancer Res 68 2008 1935 1944
191. J.P. Rodrigo, G. Alvarez-Alija, S.T. Menendez, G. Mancebo, E. Allonca, and D. Garcia-Carracedo Cortactin and focal adhesion kinase as predictors of cancer risk in patients with laryngeal premalignancy Cancer Prev Res (Phila) 4 2011 1333 1341
192. J.P. Rodrigo, F. Dominguez, V. Suarez, M. Canel, P. Secades, and M.D. Chiara Focal adhesion kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer Arch Otolaryngol Head Neck Surg 133 2007 145 150
193. L.H. Romer, N. McLean, C.E. Turner, and K. Burridge Tyrosine kinase activity, cytoskeletal organization, and motility in human vascular endothelial cells Mol Biol Cell 5 1994 349 361
194. Y. Saito, S. Mori, K. Yokote, T. Kanzaki, Y. Saito, and N. Morisaki Phosphatidylinositol 3-kinase activity is required for the activation process of focal adhesion kinase by platelet-derived growth factor Biochem Biophys Res Commun 224 1996 23 26
195. K. Sakurama, K. Noma, M. Takaoka, Y. Tomono, N. Watanabe, and S. Hatakeyama Inhibition of focal adhesion kinase as a potential therapeutic strategy for imatinib-resistant gastrointestinal stromal tumor Mol Cancer Ther 8 2009 127 134
196. E.P. Salazar, and E. Rozengurt Src family kinases are required for integrin-mediated but not for G protein-coupled receptor stimulation of focal adhesion kinase autophosphorylation at Tyr-397 J Biol Chem 276 2001 17788 17795
197. M.S. Samuel, J.I. Lopez, E.J. McGhee, D.R. Croft, D. Strachan, and P. Timpson Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth Cancer Cell 19 2011 776 791
198. E. Sandilands, B. Serrels, D.G. McEwan, J.P. Morton, J.P. Macagno, and K. McLeod Autophagic targeting of Src promotes cancer cell survival following reduced FAK signalling Nat Cell Biol 14 2012 51 60
199. E. Sandilands, B. Serrels, S. Wilkinson, and M.C. Frame Src-dependent autophagic degradation of Ret in FAK-signalling-defective cancer cells EMBO Rep 13 2012 733 740
200. M.D. Schaller Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions J Cell Sci 123 2010 1007 1013
201. M.D. Schaller, C.A. Borgman, B.S. Cobb, R.R. Vines, A.B. Reynolds, and J.T. Parsons pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions Proc Natl Acad Sci U S A 89 1992 5192 5196
202. M.D. Schaller, J.D. Hildebrand, J.D. Shannon, J.W. Fox, R.R. Vines, and J.T. Parsons Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src Mol Cell Biol 14 1994 1680 1688
203. D.M. Scheswohl, J.R. Harrell, Z. Rajfur, G. Gao, S.L. Campbell, and M.D. Schaller Multiple paxillin binding sites regulate FAK function J Mol Signal 3 2008 1
204. D.D. Schlaepfer, M.A. Broome, and T. Hunter Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: involvement of the Grb2, p130cas, and Nck adaptor proteins Mol Cell Biol 17 1997 1702 1713
205. D.D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase Nature 372 1994 786 791
206. D.D. Schlaepfer, C.R. Hauck, and D.J. Sieg Signaling through focal adhesion kinase Prog Biophys Mol Biol 71 1999 435 478
207. G.B. Schneider, Z. Kurago, R. Zaharias, L.M. Gruman, M.D. Schaller, and M.J. Hendrix Elevated focal adhesion kinase expression facilitates oral tumor cell invasion Cancer 95 2002 2508 2515
208. A. Schultze, and W. Fiedler Therapeutic potential and limitations of new FAK inhibitors in the treatment of cancer Expert Opin Investig Drugs 19 2010 777 788
209. J.L. Sechler, and J.E. Schwarzbauer Control of cell cycle progression by fibronectin matrix architecture J Biol Chem 273 1998 25533 25536
210. J. Seong, M. Ouyang, T. Kim, J. Sun, P.C. Wen, and S. Lu Detection of focal adhesion kinase activation at membrane microdomains by fluorescence resonance energy transfer Nat Commun 2 2011 406
211. A. Serrels, K. McLeod, M. Canel, A. Kinnaird, K. Graham, and M.C. Frame The role of focal adhesion kinase catalytic activity on the proliferation and migration of squamous cell carcinoma cells Int J Cancer 131 2012 287 297
212. B. Serrels, E. Sandilands, and M.C. Frame Signaling of the direction-sensing FAK/RACK1/PDE4D5 complex to the small GTPase Rap1 Small GTPases 2 2011 54 61
213. B. Serrels, A. Serrels, V.G. Brunton, M. Holt, G.W. McLean, and C.H. Gray Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex Nat Cell Biol 9 2007 1046 1056
214. A. Serrels, P. Timpson, M. Canel, J.P. Schwarz, N.O. Carragher, and M.C. Frame Real-time study of E-cadherin and membrane dynamics in living animals: implications for disease modeling and drug development Cancer Res 69 2009 2714 2719
215. N.R. Shah, I. Tancioni, K.K. Ward, C. Lawson, X.L. Chen, and C. Jean Analyses of merlin/NF2 connection to FAK inhibitor responsiveness in serous ovarian cancer Gynecol Oncol 134 2014 104 111
216. I.M. Shapiro, V.N. Kolev, C.M. Vidal, Y. Kadariya, J.E. Ring, and Q. Wright Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship Sci Transl Med 6 2014 237ra268
217. T.L. Shen, and J.L. Guan Differential regulation of cell migration and cell cycle progression by FAK complexes with Src, PI3K, Grb7 and Grb2 in focal contacts FEBS Lett 499 2001 176 181
218. Q. Shi, A.B. Hjelmeland, S.T. Keir, L. Song, S. Wickman, and D. Jackson A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth Mol Carcinog 46 2007 488 496
219. K. Shibata, F. Kikkawa, A. Nawa, A.A. Thant, K. Naruse, and S. Mizutani Both focal adhesion kinase and c-Ras are required for the enhanced matrix metalloproteinase 9 secretion by fibronectin in ovarian cancer cells Cancer Res 58 1998 900 903
220. D.J. Sieg, C.R. Hauck, D. Ilic, C.K. Klingbeil, E. Schaefer, and C.H. Damsky FAK integrates growth-factor and integrin signals to promote cell migration Nat Cell Biol 2 2000 249 256
221. D.J. Sieg, C.R. Hauck, and D.D. Schlaepfer Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration J Cell Sci 112 Pt 16 1999 2677 2691
222. J.K. Slack-Davis, K.H. Martin, R.W. Tilghman, M. Iwanicki, E.J. Ung, and C. Autry Cellular characterization of a novel focal adhesion kinase inhibitor J Biol Chem 282 2007 14845 14852
223. Y. Sonoda, T. Kasahara, E. Yokota-Aizu, M. Ueno, and S. Watanabe A suppressive role of p125FAK protein tyrosine kinase in hydrogen peroxide-induced apoptosis of T98G cells Biochem Biophys Res Commun 241 1997 769 774
224. Y. Sonoda, Y. Matsumoto, M. Funakoshi, D. Yamamoto, S.K. Hanks, and T. Kasahara Anti-apoptotic role of focal adhesion kinase (FAK). Induction of inhibitor-of-apoptosis proteins and apoptosis suppression by the overexpression of FAK in a human leukemic cell line, HL-60 J Biol Chem 275 2000 16309 16315
225. Y. Sonoda, S. Watanabe, Y. Matsumoto, E. Aizu-Yokota, and T. Kasahara FAK is the upstream signal protein of the phosphatidylinositol 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis of a human glioblastoma cell line J Biol Chem 274 1999 10566 10570
226. A.K. Sood, G.N. Armaiz-Pena, J. Halder, A.M. Nick, R.L. Stone, and W. Hu Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis J Clin Invest 120 2010 1515 1523
227. A.K. Sood, J.E. Coffin, G.B. Schneider, M.S. Fletcher, B.R. DeYoung, and L.M. Gruman Biological significance of focal adhesion kinase in ovarian cancer: role in migration and invasion Am J Pathol 165 2004 1087 1095
228. J.-C. Soria, H.K. Gan, H.-T. Arkenau, S.P. Blagden, R. Plummer, and M. Ranson Phase I clinical and pharmacologic study of the focal adhesion kinase (FAK) inhibitor GSK2256098 in pts with advanced solid tumors J Clin Oncol 30 2012 (Suppl.; abstr 3000)
229. J.B. Stokes, S.J. Adair, J.K. Slack-Davis, D.M. Walters, R.W. Tilghman, and E.D. Hershey Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment Mol Cancer Ther 10 2011 2135 2145
230. R.L. Stone, K.A. Baggerly, G.N. Armaiz-Pena, Y. Kang, A.M. Sanguino, and D. Thanapprapasr Focal adhesion kinase: an alternative focus for anti-angiogenesis therapy in ovarian cancer Cancer Biol Ther 15 2014 919 929
231. J.M. Su, L. Gui, Y.P. Zhou, and X.L. Zha Expression of focal adhesion kinase and alpha5 and beta1 integrins in carcinomas and its clinical significance World J Gastroenterol 8 2002 613 618
232. M.C. Subauste, O. Pertz, E.D. Adamson, C.E. Turner, S. Junger, and K.M. Hahn Vinculin modulation of paxillin-FAK interactions regulates ERK to control survival and motility J Cell Biol 165 2004 371 381
233. F.J. Sulzmaier, C. Jean, and D.D. Schlaepfer FAK in cancer: mechanistic findings and clinical applications Nat Rev Cancer 14 2014 598 610
234. H. Sun, S. Pisle, E.R. Gardner, and W.D. Figg Bioluminescent imaging study: FAK inhibitor, PF-562,271, preclinical study in PC3M-luc-C6 local implant and metastasis xenograft models Cancer Biol Ther 10 2010 38 43
235. K. Tachibana, T. Sato, N. D'Avirro, and C. Morimoto Direct association of pp125FAK with paxillin, the focal adhesion-targeting mechanism of pp125FAK J Exp Med 182 1995 1089 1099
236. R. Takahashi, Y. Sonoda, D. Ichikawa, N. Yoshida, A.Y. Eriko, and K. Tadashi Focal adhesion kinase determines the fate of death or survival of cells in response to TNFalpha in the presence of actinomycin D Biochim Biophys Acta 1770 2007 518 526
237. H. Tang, A. Li, J. Bi, D.M. Veltman, T. Zech, and H.J. Spence Loss of Scar/WAVE complex promotes N-WASP- and FAK-dependent invasion Curr Biol 23 2013 107 117
238. I. Tanjoni, C. Walsh, S. Uryu, A. Tomar, J.O. Nam, and A. Mielgo PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments Cancer Biol Ther 9 2010 764 777
239. B. Tavora, S. Batista, L.E. Reynolds, S. Jadeja, S. Robinson, and V. Kostourou Endothelial FAK is required for tumour angiogenesis EMBO Mol Med 2 2010 516 528
240. B. Tavora, L.E. Reynolds, S. Batista, F. Demircioglu, I. Fernandez, and T. Lechertier Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy Nature 514 2014 112 116
241. J.M. Taylor, C.P. Mack, K. Nolan, C.P. Regan, G.K. Owens, and J.T. Parsons Selective expression of an endogenous inhibitor of FAK regulates proliferation and migration of vascular smooth muscle cells Mol Cell Biol 21 2001 1565 1572
242. S.E. Theocharis, J.T. Klijanienko, E. Padoy, S. Athanassiou, and X.X. Sastre-Garau Focal adhesion kinase (FAK) immunocytochemical expression in breast ductal invasive carcinoma (DIC): correlation with clinicopathological parameters and tumor proliferative capacity Med Sci Monit 15 2009 BR221 BR226
243. J.P. Thiery, and J.P. Sleeman Complex networks orchestrate epithelial-mesenchymal transitions Nat Rev Mol Cell Biol 7 2006 131 142
244. R.W. Tilghman, J.K. Slack-Davis, N. Sergina, K.H. Martin, M. Iwanicki, and E.D. Hershey Focal adhesion kinase is required for the spatial organization of the leading edge in migrating cells J Cell Sci 118 2005 2613 2623
245. P. Timpson, G.E. Jones, M.C. Frame, and V.G. Brunton Coordination of cell polarization and migration by the Rho family GTPases requires Src tyrosine kinase activity Curr Biol 11 2001 1836 1846
246. A. Tomar, S.T. Lim, Y. Lim, and D.D. Schlaepfer A FAK-p120RasGAP-p190RhoGAP complex regulates polarity in migrating cells J Cell Sci 122 2009 1852 1862
247. A. Tomar, and D.D. Schlaepfer Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility Curr Opin Cell Biol 21 2009 676 683
248. L. Tremblay, W. Hauck, A.G. Aprikian, L.R. Begin, A. Chapdelaine, and S. Chevalier Focal adhesion kinase (pp125FAK) expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma Int J Cancer 68 1996 164 171
249. M. Tsujioka, L.M. Machesky, S.L. Cole, K. Yahata, and K. Inouye A unique talin homologue with a villin headpiece-like domain is required for multicellular morphogenesis in Dictyostelium Curr Biol 9 1999 389 392
250. D.A. Ucar, E. Kurenova, T.J. Garrett, W.G. Cance, C. Nyberg, and A. Cox Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth Cell Cycle 11 2012 3250 3259
251. D.A. Ucar, A.T. Magis, D.H. He, N.J. Lawrence, S.M. Sebti, and E. Kurenova Inhibiting the interaction of cMET and IGF-1R with FAK effectively reduces growth of pancreatic cancer cells in vitro and in vivo Anticancer Agents Med Chem 13 2013 595 602
252. M.H. van Miltenburg, M.J. van Nimwegen, I. Tijdens, R. Lalai, R. Kuiper, and S. Klarenbeek Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation Br J Cancer 110 2014 2747 2755
253. T. Veikkola, M. Karkkainen, L. Claesson-Welsh, and K. Alitalo Regulation of angiogenesis via vascular endothelial growth factor receptors Cancer Res 60 2000 203 212
254. J.E. Visvader, and G.J. Lindeman Cancer stem cells in solid tumours: accumulating evidence and unresolved questions Nat Rev Cancer 8 2008 755 768
255. C. Walsh, I. Tanjoni, S. Uryu, A. Tomar, J.O. Nam, and H. Luo Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models Cancer Biol Ther 9 2010 778 790
256. Y. Wang, and M.A. McNiven Invasive matrix degradation at focal adhesions occurs via protease recruitment by a FAK-p130Cas complex J Cell Biol 196 2012 375 385
257. K.K. Ward, I. Tancioni, C. Lawson, N.L. Miller, C. Jean, and X.L. Chen Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression Clin Exp Metastasis 30 2013 579 594
258. N. Watanabe, M. Takaoka, K. Sakurama, Y. Tomono, S. Hatakeyama, and O. Ohmori Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth factor-I receptor exhibits anticancer effect in esophageal adenocarcinoma in vitro and in vivo Clin Cancer Res 14 2008 4631 4639
259. D.J. Webb, K. Donais, L.A. Whitmore, S.M. Thomas, C.E. Turner, and J.T. Parsons FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly Nat Cell Biol 6 2004 154 161
260. J.F. Wei, L. Wei, X. Zhou, Z.Y. Lu, K. Francis, and X.Y. Hu Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility J Cell Physiol 217 2008 544 557
261. T.M. Weiner, E.T. Liu, R.J. Craven, and W.G. Cance Expression of focal adhesion kinase gene and invasive cancer Lancet 342 1993 1024 1025
262. H.G. Wendel, E. De Stanchina, J.S. Fridman, A. Malina, S. Ray, and S. Kogan Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy Nature 428 2004 332 337
263. X. Wu, B. Gan, Y. Yoo, and J.L. Guan FAK-mediated src phosphorylation of endophilin A2 inhibits endocytosis of MT1-MMP and promotes ECM degradation Dev Cell 9 2005 185 196
264. X. Wu, S. Suetsugu, L.A. Cooper, T. Takenawa, and J.L. Guan Focal adhesion kinase regulation of N-WASP subcellular localization and function J Biol Chem 279 2004 9565 9576
265. Z.M. Wu, X.H. Yuan, P.C. Jiang, Z.Q. Li, and T. Wu Antisense oligonucleodes targeting the focal adhesion kinase inhibit proliferation, induce apoptosis and cooperate with cytotoxic drugs in human glioma cells J Neurooncol 77 2006 117 123
266. L. Yao, K. Li, W. Peng, Q. Lin, S. Li, and X. Hu An aberrant spliced transcript of focal adhesion kinase is exclusively expressed in human breast cancer J Transl Med 12 2014 136
267. C.K. Yom, D.Y. Noh, W.H. Kim, and H.S. Kim Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer Breast Cancer Res Treat 128 2011 647 655
268. J.A. Yu, N.O. Deakin, and C.E. Turner Paxillin-kinase-linker tyrosine phosphorylation regulates directional cell migration Mol Biol Cell 20 2009 4706 4719
269. H.G. Yu, S.L. Tong, Y.M. Ding, J. Ding, X.M. Fang, and X.F. Zhang Enhanced expression of cholecystokinin-2 receptor promotes the progression of colon cancer through activation of focal adhesion kinase Int J Cancer 119 2006 2724 2732
270. L. Zeng, X. Si, W.P. Yu, H.T. Le, K.P. Ng, and R.M. Teng PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration J Cell Biol 160 2003 137 146
271. J. Zhai, H. Lin, Z. Nie, J. Wu, R. Canete-Soler, and W.W. Schlaepfer Direct interaction of focal adhesion kinase with p190RhoGEF J Biol Chem 278 2003 24865 24873
272. J. Zhao, R. Pestell, and J.L. Guan Transcriptional activation of cyclin D1 promoter by FAK contributes to cell cycle progression Mol Biol Cell 12 2001 4066 4077
273. J.H. Zhao, H. Reiske, and J.L. Guan Regulation of the cell cycle by focal adhesion kinase J Cell Biol 143 1998 1997 2008
274. Y. Zheng, J. Gierut, Z. Wang, J. Miao, J.M. Asara, and A.L. Tyner Protein tyrosine kinase 6 protects cells from anoikis by directly phosphorylating focal adhesion kinase and activating AKT Oncogene 32 2013 4304 4312
275. D. Zheng, V. Golubovskaya, E. Kurenova, C. Wood, N.A. Massoll, and D. Ostrov A novel strategy to inhibit FAK and IGF-1R decreases growth of pancreatic cancer xenografts Mol Carcinog 49 2010 200 209
276. N.K. Zouq, J.A. Keeble, J. Lindsay, A.J. Valentijn, L. Zhang, and D. Mills FAK engages multiple pathways to maintain survival of fibroblasts and epithelia: differential roles for paxillin and p130Cas J Cell Sci 122 2009 357 367