Focal adhesion signaling and therapy resistance in cancer

Seminars in Cancer Biology

Volumn 31, Issue , 2015, Pages 65-75

  Eke, Iris ^a,b   Cordes, Nils ^a,b,c  

^a UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^b INSTITUTE OF ION BEAM PHYSICS AND MATERIALS RESEARCH   (Germany)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Extracellular matrix; Focal adhesion; Integrins; Small molecules; Targeted therapy

Indexed keywords

AG 957; ALPHA4 INTEGRIN; ALPHA6BETA4 INTEGRIN; ANTINEOPLASTIC AGENT; ARAC PROTEIN; BETA4 INTEGRIN; CETUXIMAB; CISPLATIN; DEXAMETHASONE; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ETOPOSIDE; FIBRONECTIN; FOCAL ADHESION KINASE; GELATINASE A; IMATINIB; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN P53; STAT3 PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VERY LATE ACTIVATION ANTIGEN 2; VERY LATE ACTIVATION ANTIGEN 3; VERY LATE ACTIVATION ANTIGEN 5; VINCRISTINE; VITRONECTIN RECEPTOR; INTEGRIN;

ANOIKIS; ANTIPROLIFERATIVE ACTIVITY; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER SURVIVAL; CARCINOGENESIS; CELL DEATH; CELL DIFFERENTIATION; CELL INTERACTION; CELL MIGRATION; CELL SURVIVAL; CHEMORADIOTHERAPY; CYTOSKELETON; DOWN REGULATION; ENZYME ACTIVITY; FOCAL ADHESION; HUMAN; METASTASIS; NONHUMAN; OVERALL SURVIVAL; PROTEIN BINDING; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR MICROENVIRONMENT; UPREGULATION; BIOLOGICAL MODEL; CELL ADHESION; DISEASE COURSE; EXTRACELLULAR MATRIX; METABOLISM; NEOPLASMS; PATHOLOGY;

CELL ADHESION; DISEASE PROGRESSION; EXTRACELLULAR MATRIX; FOCAL ADHESIONS; HUMANS; INTEGRINS; MODELS, BIOLOGICAL; NEOPLASM METASTASIS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84923184180     PISSN: 1044579X     EISSN: 10963650     Source Type: Journal    
DOI: 10.1016/j.semcancer.2014.07.009     Document Type: Review

References (199)

1. Ferlay J., Shin H-R., Bray F., Forman D., Mathers C., Parkin D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127:2893-2917.
2. Mathers C.D., Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006, 3:e442.
3. Cordes N., Meineke V. Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro. Strahlenther Onkol 2003, 179:337-344.
4. Sandfort V., Koch U., Cordes N. Cell adhesion-mediated radioresistance revisited. Int J Radiat Biol 2007, 83:727-732.
5. Damiano J.S., Hazlehurst L.A., Dalton W.S. Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition, cytotoxic drugs, and gamma-irradiation. Leukemia 2001, 15:1232-1239.
6. Hazlehurst L.A., Damiano J.S., Buyuksal I., Pledger W.J., Dalton W.S. Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene 2000, 19:4319-4327.
7. Damiano J.S., Cress A.E., Hazlehurst L.A., Shtil A.A., Dalton W.S. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 1999, 93:1658-1667.
8. Landowski T.H., Olashaw N.E., Agrawal D., Dalton W.S. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene 2003, 22:2417-2421.
9. Hazlehurst L.A., Argilagos R.F., Emmons M., Boulware D., Beam C.A., Sullivan D.M., et al. Cell adhesion to fibronectin (CAM-DR) influences acquired mitoxantrone resistance in U937 cells. Cancer Res 2006, 66:2338-2345.
10. Meads M.B., Gatenby R.A., Dalton W.S. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer 2009, 9:665-674.
11. Legate K.R., Fässler R. Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails. J Cell Sci 2009, 122:187-198.
12. Legate K.R., Wickström S.A., Fässler R. Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev 2009, 23:397-418.
13. Vehlow A., Cordes N. Invasion as target for therapy of glioblastoma multiforme. Biochim Biophys Acta 2013, 1836:236-244.
14. Park C.C., Zhang H., Pallavicini M., Gray J.W., Baehner F., Park C.J., et al. Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Res 2006, 66:1526-1535.
15. Park C.C., Zhang H.J., Yao E.S., Park C.J., Bissell M.J. Beta1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts. Cancer Res 2008, 68:4398-4405.
16. Eke I., Deuse Y., Hehlgans S., Gurtner K., Krause M., Baumann M., et al. β1 Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy. J Clin Invest 2012, 122:1529-1540.
17. Eke I., Dickreuter E., Cordes N. Enhanced radiosensitivity of head and neck squamous cell carcinoma cells by β1 integrin inhibition. Radiother Oncol 2012, 104:235-242.
18. Nam J-M., Onodera Y., Bissell M.J., Park C.C. Breast cancer cells in three-dimensional culture display an enhanced radioresponse after coordinate targeting of integrin alpha5beta1 and fibronectin. Cancer Res 2010, 70:5238-5248.
19. Eke I., Storch K., Krause M., Cordes N. Cetuximab attenuates its cytotoxic and radiosensitizing potential by inducing fibronectin biosynthesis. Cancer Res 2013, 73:5869-5879.
20. Eke I., Schneider L., Förster C., Zips D., Kunz-Schughart L.A., Cordes N. EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells. Cancer Res 2013, 73:297-306.
21. Lesniak D., Xu Y., Deschenes J., Lai R., Thoms J., Murray D., et al. Beta1-integrin circumvents the antiproliferative effects of trastuzumab in human epidermal growth factor receptor-2-positive breast cancer. Cancer Res 2009, 69:8620-8628.
22. Hynes R.O. Integrins: bidirectional, allosteric signaling machines. Cell 2002, 110:673-687.
23. Humphries J.D., Byron A., Humphries M.J. Integrin ligands at a glance. J Cell Sci 2006, 119:3901-3903.
24. Brakebusch C., Fässler R. beta 1 integrin function in vivo: adhesion, migration and more. Cancer Metastasis Rev 2005, 24:403-411.
25. Hehlgans S., Haase M., Cordes N. Signalling via integrins: implications for cell survival and anticancer strategies. Biochim Biophys Acta 2007, 1775:163-180.
26. Ross T.D., Coon B.G., Yun S., Baeyens N., Tanaka K., Ouyang M., et al. Integrins in mechanotransduction. Curr Opin Cell Biol 2013, 25:613-618.
27. LaFlamme S.E., Auer K.L. Integrin signaling. Semin Cancer Biol 1996, 7:111-118.
28. Calderwood D.A., Campbell I.D., Critchley D.R. Talins and kindlins: partners in integrin-mediated adhesion. Nat Rev Mol Cell Biol 2013, 14:503-517.
29. Janes S.M., Watt F.M. New roles for integrins in squamous-cell carcinoma. Nat Rev Cancer 2006, 6:175-183.
30. Tennenbaum T., Weiner A.K., Belanger A.J., Glick A.B., Hennings H., Yuspa S.H. The suprabasal expression of {alpha}6{beta}4 integrin is associated with a high risk for malignant progression in mouse skin carcinogenesis. Cancer Res 1993, 53:4803-4810.
31. Tennenbaum T., Yuspa S.H., Grover A., Castronovo V., Sobel M.E., Yamada Y., et al. Extracellular matrix receptors and mouse skin carcinogenesis: altered expression linked to appearance of early markers of tumor progression. Cancer Res 1992, 52:2966-2976.
32. Guo W., Pylayeva Y., Pepe A., Yoshioka T., Muller W.J., Inghirami G., et al. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 2006, 126:489-502.
33. Carico E., French D., Bucci B., Falcioni R., Vecchione A., Mariani-Costantini R. Integrin beta 4 expression in the neoplastic progression of cervical epithelium. Gynecol Oncol 1993, 49:61-66.
34. Zutter M.M., Santoro S.A., Staatz W.D., Tsung Y.L. Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells. Proc Natl Acad Sci 1995, 92:7411-7415.
35. Sachs N., Secades P., van Hulst L., Kreft M., Song J-Y., Sonnenberg A. Loss of integrin α3 prevents skin tumor formation by promoting epidermal turnover and depletion of slow-cycling cells. Proc Natl Acad Sci U S A 2012, 109:21468-21473.
36. Moreno-Layseca P., Streuli C.H. Signalling pathways linking integrins with cell cycle progression. Matrix Biol 2014, 34C:144-153.
37. Duperret E.K., Ridky T.W. Focal adhesion complex proteins in epidermis and squamous cell carcinoma. Cell Cycle 2013, 12:3272-3285.
38. Christofori G. Changing neighbours, changing behaviour: cell adhesion molecule-mediated signalling during tumour progression. EMBO J 2003, 22:2318-2323.
39. Stoeltzing O., Liu W., Reinmuth N., Fan F., Parry G.C., Parikh A.A., et al. Inhibition of integrin alpha5beta1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice. Int J Cancer 2003, 104:496-503.
40. Dutta A., Li J., Lu H., Akech J., Pratap J., Wang T., et al. Integrin αvβ6 promotes an osteolytic program in cancer cells by upregulating MMP2. Cancer Res 2014, 74:1598-1608.
41. Felding-Habermann B., O'Toole T.E., Smith J.W., Fransvea E., Ruggeri Z.M., Ginsberg M.H., et al. Integrin activation controls metastasis in human breast cancer. Proc Natl Acad Sci U S A 2001, 98:1853-1858.
42. Pécheur I., Peyruchaud O., Serre C-M., Guglielmi J., Voland C., Bourre F., et al. Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone. FASEB J 2002, 16:1266-1268.
43. Wang H., Fu W., Im J.H., Zhou Z., Santoro S.A., Iyer V., et al. Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J Cell Biol 2004, 164:935-941.
44. Kren A., Baeriswyl V., Lehembre F., Wunderlin C., Strittmatter K., Antoniadis H., et al. Increased tumor cell dissemination and cellular senescence in the absence of beta1-integrin function. EMBO J 2007, 26:2832-2842.
45. Aguirre-Ghiso J.A. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 2007, 7:834-846.
46. Pontier S.M., Muller W.J. Integrins in mammary-stem-cell biology and breast-cancer progression-a role in cancer stem cells?. J Cell Sci 2009, 122:207-214.
47. Visvader J.E., Lindeman G.J. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 2008, 8:755-768.
48. Cojoc M., Mäbert K., Muders M.H., Dubrovska A. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. Semin Cancer Biol 2014, 10.1016/j.semcancer.2014.06.004.
49. Korah R., Boots M., Wieder R. Integrin alpha5beta1 promotes survival of growth-arrested breast cancer cells: an in vitro paradigm for breast cancer dormancy in bone marrow. Cancer Res 2004, 64:4514-4522.
50. Aguirre Ghiso J.A. Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J Cell Biol 1999, 147:89-104.
51. Aguirre Ghiso J.A. Inhibition of FAK signaling activated by urokinase receptor induces dormancy in human carcinoma cells in vivo. Oncogene 2002, 21:2513-2524.
52. Najmi S., Korah R., Chandra R., Abdellatif M., Wieder R. Flavopiridol blocks integrin-mediated survival in dormant breast cancer cells. Clin Cancer Res 2005, 11:2038-2046.
53. Frantz C., Stewart K.M., Weaver V.M. The extracellular matrix at a glance. J Cell Sci 2010, 123:4195-4200.
54. Lu P., Weaver V.M., Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 2012, 196:395-406.
55. Paszek M.J., Zahir N., Johnson K.R., Lakins J.N., Rozenberg G.I., Gefen A., et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 2005, 8:241-254.
56. Tanentzapf G., Devenport D., Godt D., Brown N.H. Integrin-dependent anchoring of a stem-cell niche. Nat Cell Biol 2007, 9:1413-1418.
57. Cox T.R., Erler J.T. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis Model Mech 2011, 4:165-178.
58. Levental K.R., Yu H., Kass L., Lakins J.N., Egeblad M., Erler J.T., et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 2009, 139:891-906.
59. Mott J.D., Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 2004, 16:558-564.
60. Raymond K., Deugnier M-A., Faraldo M.M., Glukhova M.A. Adhesion within the stem cell niches. Curr Opin Cell Biol 2009, 21:623-629.
61. Radisky E.S., Radisky D.C. Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J Mammary Gland Biol Neoplasia 2010, 15:201-212.
62. Pattabiraman D.R., Weinberg R.A. Tackling the cancer stem cells-what challenges do they pose?. Nat Rev Drug Discov 2014, 13:497-512.
63. Friedrichs K., Ruiz P., Franke F., Gille I., Terpe H-J., Imhof B.A. High expression level of {alpha}6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res 1995, 55:901-906.
64. Albelda S.M., Mette S.A., Elder D.E., Stewart R., Damjanovich L., Herlyn M., et al. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res 1990, 50:6757-6764.
65. Adachi M., Taki T., Higashiyama M., Kohno N., Inufusa H., Miyake M. Significance of integrin alpha5 gene expression as a prognostic factor in node-negative non-small cell lung cancer. Clin Cancer Res 2000, 6:96-101.
66. Gladson C.L., Cheresh D.A. Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells. J Clin Invest 1991, 88:1924-1932.
67. Eriksen J.G., Steiniche T., Søgaard H., Overgaard J. Expression of integrins and E-cadherin in squamous cell carcinomas of the head and neck. APMIS 2004, 112:560-568.
68. 18F] Galacto-RGD positron emission tomography. Neuro Oncol 2009, 11:861-870.
69. Schottelius M., Laufer B., Kessler H., Wester H-J. Ligands for mapping alphavbeta3-integrin expression in vivo. Acc Chem Res 2009, 42:969-980.
70. Eisele G., Wick A., Eisele A-C., Clément P.M., Tonn J., Tabatabai G., et al. Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. J Neurooncol 2014, 117:141-145.
71. Tabatabai G., Weller M., Nabors B., Picard M., Reardon D., Mikkelsen T., et al. Targeting integrins in malignant glioma. Target Oncol 2010, 5:175-181.
72. Reardon D.A., Neyns B., Weller M., Tonn J-C., Nabors L.B., Stupp R. Cilengitide: an RGD pentapeptide αvβ3 and αvβ5 integrin inhibitor in development for glioblastoma and other malignancies. Futur Oncol 2011, 7:339-354.
73. Eke I., Storch K., Kästner I., Vehlow A., Faethe C., Mueller-Klieser W., et al. Three-dimensional invasion of human glioblastoma cells remains unchanged by X-ray and carbon ion irradiation in vitro. Int J Radiat Oncol Biol Phys 2012, 84:e515-e523.
74. Bhaskar V., Zhang D., Fox M., Seto P., Wong M.H.L., Wales P.E., et al. A function blocking anti-mouse integrin alpha5beta1 antibody inhibits angiogenesis and impedes tumor growth in vivo. J Transl Med 2007, 5:61.
75. Cordes N., Hansmeier B., Beinke C., Meineke V., van Beuningen D. Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines. Br J Cancer 2003, 89:2122-2132.
76. Cordes N., Frick S., Brunner T.B., Pilarsky C., Grützmann R., Sipos B., et al. Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1. Oncogene 2007, 26:6851-6862.
77. Hehlgans S., Eke I., Storch K., Haase M., Baretton G.B., Cordes N. Caveolin-1 mediated radioresistance of 3D grown pancreatic cancer cells. Radiother Oncol 2009, 92:362-370.
78. Estrugo D., Fischer A., Hess F., Scherthan H., Belka C., Cordes N. Ligand bound beta1 integrins inhibit procaspase-8 for mediating cell adhesion-mediated drug and radiation resistance in human leukemia cells. PLoS ONE 2007, 2:e269.
79. Monferran S., Skuli N., Delmas C., Favre G., Bonnet J., Cohen-Jonathan-Moyal E., et al. Alphavbeta3 and alphavbeta5 integrins control glioma cell response to ionising radiation through ILK and RhoB. Int J Cancer 2008, 123:357-364.
80. Mantoni T.S., Lunardi S., Al-Assar O., Masamune A., Brunner T.B. Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling. Cancer Res 2011, 71:3453-3458.
81. Cao Q., Cai W., Li T., Yang Y., Chen K., Xing L., et al. Combination of integrin siRNA and irradiation for breast cancer therapy. Biochem Biophys Res Commun 2006, 351:726-732.
82. Goel H.L., Sayeed A., Breen M., Zarif M.J., Garlick D.S., Leav I., et al. β1 integrins mediate resistance to ionizing radiation in vivo by inhibiting c-Jun amino terminal kinase 1. J Cell Physiol 2013, 228:1601-1609.
83. Ou J., Luan W., Deng J., Sa R., Liang H. αV integrin induces multicellular radioresistance in human nasopharyngeal carcinoma via activating SAPK/JNK pathway. PLoS ONE 2012, 7:e38737.
84. Albert M., Schmidt M., Cordes N., Dörr W. Modulation of radiation-induced oral mucositis (mouse) by selective inhibition of β1 integrin. Radiother Oncol 2012, 104:230-234.
85. Cordes N., Blaese M.A., Meineke V., Van Beuningen D. Ionizing radiation induces up-regulation of functional beta1-integrin in human lung tumour cell lines in vitro. Int J Radiat Biol 2002, 78:347-357.
86. Yao H., Zeng Z-Z., Fay K.S., Veine D.M., Staszewski E.D., Morgan M., et al. Role of α(5)β(1) integrin up-regulation in radiation-induced invasion by human pancreatic cancer cells. Transl Oncol 2011, 4:282-292.
87. Ahmed K.M., Zhang H., Park C.C. NF-κB regulates radioresistance mediated by β1-integrin in three-dimensional culture of breast cancer cells. Cancer Res 2013, 73:3737-3748.
88. Cheng J.C-H., Chou C.H., Kuo M.L., Hsieh C-Y. Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway. Oncogene 2006, 25:7009-7018.
89. Park C-M., Park M-J., Kwak H-J., Lee H-C., Kim M-S., Lee S-H., et al. Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways. Cancer Res 2006, 66:8511-8519.
90. Zhao W., Goswami P.C., Robbins M.E.C. Radiation-induced up-regulation of Mmp2 involves increased mRNA stability, redox modulation, and MAPK activation. Radiat Res 2004, 161:418-429.
91. Barcellos-Hoff M.H., Ravani S.A. Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res 2000, 60:1254-1260.
92. Barcellos-Hoff M.H., Park C., Wright E.G. Radiation and the microenvironment-tumorigenesis and therapy. Nat Rev Cancer 2005, 5:867-875.
93. Mahadevan D., Von Hoff D.D. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 2007, 6:1186-1197.
94. Damiano J.S., Dalton W.S. Integrin-mediated drug resistance in multiple myeloma. Leuk Lymphoma 2000, 38:71-81.
95. Hodkinson P.S., Elliott T., Wong W.S., Rintoul R.C., Mackinnon A.C., Haslett C., et al. ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Cell Death Differ 2006, 13:1776-1788.
96. Martinkova E., Maglott A., Leger D.Y., Bonnet D., Stiborova M., Takeda K., et al. alpha5beta1 integrin antagonists reduce chemotherapy-induced premature senescence and facilitate apoptosis in human glioblastoma cells. Int J Cancer 2010, 127:1240-1248.
97. Zhang H., Ozaki I., Mizuta T., Matsuhashi S., Yoshimura T., Hisatomi A., et al. Beta 1-integrin protects hepatoma cells from chemotherapy induced apoptosis via a mitogen-activated protein kinase dependent pathway. Cancer 2002, 95:896-906.
98. Sethi T., Rintoul R.C., Moore S.M., MacKinnon A.C., Salter D., Choo C., et al. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med 1999, 5:662-668.
99. Andjilani M., Droz J-P., Benahmed M., Tabone E. Alpha6 integrin subunit mediates laminin enhancement of cisplatin-induced apoptosis in testicular tumor germ cells. Int J Cancer 2005, 117:68-81.
100. Mori R., Ishiguro H., Kuwabara Y., Kimura M., Mitsui A., Tomoda K., et al. Targeting β1 integrin restores sensitivity to docetaxel of esophageal squamous cell carcinoma. Oncol Rep 2008, 20:1345-1351.
101. He J-M., Wang F-C., Qi H-B., Li Y., Liang H-J. Down-regulation of alphav integrin by retroviral delivery of small interfering RNA reduces multicellular resistance of HT29. Cancer Lett 2009, 284:182-188.
102. Layani-Bazar A., Skornick I., Berrebi A., Pauker M.H., Noy E., Silberman A., et al. Redox modulation of adjacent thiols in VLA-4 by AS101 converts myeloid leukemia cells from a drug-resistant to drug-sensitive state. Cancer Res 2014, 74:3092-3103.
103. Matsunaga T., Takemoto N., Sato T., Takimoto R., Tanaka I., Fujimi A., et al. Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med 2003, 9:1158-1165.
104. Rettig M.P., Ansstas G., DiPersio J.F. Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4. Leukemia 2012, 26:34-53.
105. Becker P.S. Dependence of acute myeloid leukemia on adhesion within the bone marrow microenvironment. Sci World J 2012, 2012:856467.
106. Hsieh Y-T., Gang E.J., Geng H., Park E., Huantes S., Chudziak D., et al. Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy. Blood 2013, 121:1814-1818.
107. Becker P.S., Kopecky K.J., Wilks A.N., Chien S., Harlan J.M., Willman C.L., et al. Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia. Blood 2009, 113:866-874.
108. Eke I., Leonhardt F., Storch K., Hehlgans S., Cordes N. The small molecule inhibitor QLT0267 radiosensitizes squamous cell carcinoma cells of the head and neck. PLoS ONE 2009, 4:e6434.
109. Storch K., Eke I., Borgmann K., Krause M., Richter C., Becker K., et al. Three-dimensional cell growth confers radioresistance by chromatin density modification. Cancer Res 2010, 70:3925-3934.
110. Eke I., Sandfort V., Mischkus A., Baumann M., Cordes N. Antiproliferative effects of EGFR tyrosine kinase inhibition and radiation-induced genotoxic injury are attenuated by adhesion to fibronectin. Radiother Oncol 2006, 80:178-184.
111. Giannelli G., Azzariti A., Sgarra C., Porcelli L., Antonaci S., Paradiso A. ZD6474 inhibits proliferation and invasion of human hepatocellular carcinoma cells. Biochem Pharmacol 2006, 71:479-485.
112. Luca A.C., Mersch S., Deenen R., Schmidt S., Messner I., Schäfer K-L., et al. Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PLoS ONE 2013, 8:e59689.
113. Eke I., Cordes N. Radiobiology goes 3D: how ECM and cell morphology impact on cell survival after irradiation. Radiother Oncol 2011, 99:271-278.
114. Schaller M.D., Borgman C.A., Cobb B.S., Vines R.R., Reynolds A.B., Parsons J.T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A 1992, 89:5192-5196.
115. Parsons J.T. Focal adhesion kinase: the first ten years. J Cell Sci 2003, 116:1409-1416.
116. Polte T.R., Hanks S.K. Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas. Proc Natl Acad Sci U S A 1995, 92:10678-10682.
117. Tomar A., Lawson C., Ghassemian M., Schlaepfer D.D. Cortactin as a target for FAK in the regulation of focal adhesion dynamics. PLoS ONE 2012, 7:e44041.
118. Miyazaki T., Kato H., Nakajima M., Sohda M., Fukai Y., Masuda N., et al. FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer 2003, 89:140-145.
119. Fujii T., Koshikawa K., Nomoto S., Okochi O., Kaneko T., Inoue S., et al. Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be served as an independent prognostic factor. J Hepatol 2004, 41:104-111.
120. Lark A.L., Livasy C.A., Dressler L., Moore D.T., Millikan R.C., Geradts J., et al. High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype. Mod Pathol 2005, 18:1289-1294.
121. Tilghman R.W., Parsons J.T. Focal adhesion kinase as a regulator of cell tension in the progression of cancer. Semin Cancer Biol 2008, 18:45-52.
122. Hehlgans S., Lange I., Eke I., Cordes N. 3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226. Radiother Oncol 2009, 92:371-378.
123. Eke I., Cordes N. Dual targeting of EGFR and focal adhesion kinase in 3D grown HNSCC cell cultures. Radiother Oncol 2011, 99:279-286.
124. Hochwald S.N., Nyberg C., Zheng M., Zheng D., Wood C., Massoll N.A., et al. A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer. Cell Cycle 2009, 8:2435-2443.
125. Roberts W.G., Ung E., Whalen P., Cooper B., Hulford C., Autry C., et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res 2008, 68:1935-1944.
126. Golubovskaya V.M., Huang G., Ho B., Yemma M., Morrison C.D., Lee J., et al. Pharmacologic blockade of FAK autophosphorylation decreases human glioblastoma tumor growth and synergizes with temozolomide. Mol Cancer Ther 2013, 12:162-172.
127. Hehlgans S., Eke I., Cordes N. Targeting FAK radiosensitizes 3-dimensional grown human HNSCC cells through reduced Akt1 and MEK1/2 signaling. Int J Radiat Oncol Biol Phys 2012, 83:e669-e676.
128. Kang Y., Hu W., Ivan C., Dalton H.J., Miyake T., Pecot C.V., et al. Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. J Natl Cancer Inst 2013, 105:1485-1495.
129. Heffler M., Golubovskaya V.M., Dunn K.M.B., Cance W. Focal adhesion kinase autophosphorylation inhibition decreases colon cancer cell growth and enhances the efficacy of chemotherapy. Cancer Biol Ther 2013, 14:761-772.
130. Golubovskaya V.M., Sumbler B., Ho B., Yemma M., Cance W.G. MiR-138 and MiR-135 directly target focal adhesion kinase, inhibit cell invasion, and increase sensitivity to chemotherapy in cancer cells. Anticancer Agents Med Chem 2014, 14:18-28.
131. Lazaro G., Smith C., Goddard L., Jordan N., McClelland R., Barrett-Lee P., et al. Targeting focal adhesion kinase in ER+/HER2+ breast cancer improves trastuzumab response. Endocr Relat Cancer 2013, 20:691-704.
132. Legate K.R., Montañez E., Kudlacek O., Fässler R.I.L.K. PINCH and parvin: the tIPP of integrin signalling. Nat Rev Mol Cell Biol 2006, 7:20-31.
133. Wickström S.A., Lange A., Montanez E., Fässler R. The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase!. EMBO J 2010, 29:281-291.
134. Qin J., Wu C. ILK: a pseudokinase in the center stage of cell-matrix adhesion and signaling. Curr Opin Cell Biol 2012, 24:607-613.
135. Eke I., Hehlgans S., Cordes N. There's something about ILK. Int J Radiat Biol 2009, 85:929-936.
136. Sakai T., Li S., Docheva D., Grashoff C., Sakai K., Kostka G., et al. Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. Genes Dev 2003, 17:926-940.
137. Hess F., Estrugo D., Fischer A., Belka C., Cordes N. Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells. Oncogene 2007, 26:1372-1384.
138. Cordes N. Overexpression of hyperactive integrin-linked kinase leads to increased cellular radiosensitivity. Cancer Res 2004, 64:5683-5692.
139. Eke I., Sandfort V., Storch K., Baumann M., Röper B., Cordes N. Pharmacological inhibition of EGFR tyrosine kinase affects ILK-mediated cellular radiosensitization in vitro. Int J Radiat Biol 2007, 83:793-802.
140. Hehlgans S., Eke I., Deuse Y., Cordes N. Integrin-linked kinase: dispensable for radiation survival of three-dimensionally cultured fibroblasts. Radiother Oncol 2008, 86:329-335.
141. Hehlgans S., Eke I., Cordes N. An essential role of integrin-linked kinase in the cellular radiosensitivity of normal fibroblasts during the process of cell adhesion and spreading. Int J Radiat Biol 2007, 83:769-779.
142. Duxbury M.S., Ito H., Benoit E., Waseem T., Ashley S.W., Whang E.E. RNA interference demonstrates a novel role for integrin-linked kinase as a determinant of pancreatic adenocarcinoma cell gemcitabine chemoresistance. Clin Cancer Res 2005, 11:3433-3438.
143. Eke I., Koch U., Hehlgans S., Sandfort V., Stanchi F., Zips D., et al. PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1alpha. J Clin Invest 2010, 120:2516-2527.
144. Sandfort V., Eke I., Cordes N. The role of the focal adhesion protein PINCH1 for the radiosensitivity of adhesion and suspension cell cultures. PLoS ONE 2010, 5:e13056.
145. Montanez E., Karaköse E., Tischner D., Villunger A., Fässler R. PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm. J Cell Sci 2012, 125:5233-5240.
146. Elias M.C., Pronovost S.M., Cahill K.J., Beckerle M.C., Kadrmas J.L. A crucial role for Ras suppressor-1 (RSU-1) revealed when PINCH and ILK binding is disrupted. J Cell Sci 2012, 125:3185-3194.
147. Dougherty G.W., Jose C., Gimona M., Cutler M., Lou The Rsu-1-PINCH1-ILK complex is regulated by Ras activation in tumor cells. Eur J Cell Biol 2008, 87:721-734.
148. Chen K., Tu Y., Zhang Y., Blair H.C., Zhang L., Wu C. PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in cancer cells. J Biol Chem 2008, 283:2508-2517.
149. Kyriakis J.M., Banerjee P., Nikolakaki E., Dai T., Rubie E.A., Ahmad M.F., et al. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 1994, 369:156-160.
150. Bode A.M., Dong Z. The functional contrariety of JNK. Mol Carcinog 2007, 46:591-598.
151. Chen Y.-R., Wang X., Templeton D., Davis R.J., Tan T.-H. The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem 1996, 271:31929-31936.
152. Reno E.M., Haughian J.M., Jackson T.A., Thorne A.M., Bradford A.P. c-Jun N-terminal kinase regulates apoptosis in endometrial cancer cells. Apoptosis 2009, 14:809-820.
153. Yoon C-H., Kim M-J., Kim R-K., Lim E-J., Choi K-S., An S., et al. c-Jun N-terminal kinase has a pivotal role in the maintenance of self-renewal and tumorigenicity in glioma stem-like cells. Oncogene 2012, 31:4655-4666.
154. Engelberg D. Stress-activated protein kinases-tumor suppressors or tumor initiators?. Semin Cancer Biol 2004, 14:271-282.
155. Oleinik N.V., Krupenko N.I., Krupenko S.A. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene 2007, 26:7222-7230.
156. Kim M-J., Lee K-H., Lee S-J. Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells. FEBS J 2008, 275:2096-2108.
157. Hennig J., McShane M.P., Cordes N., Eke I. APPL proteins modulate DNA repair and radiation survival of pancreatic carcinoma cells by regulating ATM. Cell Death Dis 2014, 5:e1199.
158. Tirado O.M., MacCarthy C.M., Fatima N., Villar J., Mateo-Lozano S., Notario V. Caveolin-1 promotes resistance to chemotherapy-induced apoptosis in Ewing's sarcoma cells by modulating PKCalpha phosphorylation. Int J Cancer 2010, 126:426-436.
159. Herzog M., Storch C.H., Gut P., Kotlyar D., Füllekrug J., Ehehalt R., et al. Knockdown of caveolin-1 decreases activity of breast cancer resistance protein (BCRP/ABCG2) and increases chemotherapeutic sensitivity. Naunyn Schmiedebergs Arch Pharmacol 2011, 383:1-11.
160. Schenck A., Goto-Silva L., Collinet C., Rhinn M., Giner A., Habermann B., et al. The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development. Cell 2008, 133:486-497.
161. Banach-Orlowska M., Pilecka I., Torun A., Pyrzynska B., Miaczynska M. Functional characterization of the interactions between endosomal adaptor protein APPL1 and the NuRD co-repressor complex. Biochem J 2009, 423:389-400.
162. Miaczynska M., Christoforidis S., Giner A., Shevchenko A., Uttenweiler-Joseph S., Habermann B., et al. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell 2004, 116:445-456.
163. Ivaska J., Heino J. Cooperation between integrins and growth factor receptors in signaling and endocytosis. Annu Rev Cell Dev Biol 2011, 27:291-320.
164. Carpenter G., Cohen S. Epidermal growth factor. Annu Rev Biochem 1979, 48:193-216.
165. ®) in non-small cell lung cancer (NSCLC). Semin Cancer Biol 2004, 14:33-40.
166. Gschwind A., Fischer O.M., Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer 2004, 4:361-370.
167. Hynes N.E., MacDonald G. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol 2009, 21:177-184.
168. Arteaga C.L., Engelman J.A. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 2014, 25:282-303.
169. Gan H.K., Cvrljevic A.N., Johns T.G. The epidermal growth factor receptor variant III (EGFRvIII): where wild things are altered. FEBS J 2013, 280:5350-5370.
170. Paez J.G., Jänne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004, 304:1497-1500.
171. Nicholson R., Gee J.M., Harper M. EGFR and cancer prognosis. Eur J Cancer 2001, 37:9-15.
172. Moroni M., Veronese S., Benvenuti S., Marrapese G., Sartore-Bianchi A., Di Nicolantonio F., et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 2005, 6:279-286.
173. Itakura Y., Sasano H., Shiga C., Furukawa Y., Shiga K., Mori S., et al. Epidermal growth factor receptor overexpression in esophageal carcinoma. An immunohistochemical study correlated with clinicopathologic findings and DNA amplification. Cancer 1994, 74:795-804.
174. Spano J-P., Lagorce C., Atlan D., Milano G., Domont J., Benamouzig R., et al. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 2005, 16:102-108.
175. Shinojima N., Tada K., Shiraishi S., Kamiryo T., Kochi M., Nakamura H., et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 2003, 63:6962-6970.
176. Yun C-H., Mengwasser K.E., Toms A.V., Woo M.S., Greulich H., Wong K-K., et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008, 105:2070-2075.
177. Greulich H., Chen T-H., Feng W., Jänne P.A., Alvarez J.V., Zappaterra M., et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PLoS Med 2005, 2:e313.
178. Cohen R.B. Current challenges and clinical investigations of epidermal growth factor receptor (EGFR)- and ErbB family-targeted agents in the treatment of head and neck squamous cell carcinoma (HNSCC). Cancer Treat Rev 2014, 40:567-577.
179. Bonner J.A., Harari P.M., Giralt J., Azarnia N., Shin D.M., Cohen R.B., et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006, 354:567-578.
180. Gurtner K., Deuse Y., Bütof R., Schaal K., Eicheler W., Oertel R., et al. Diverse effects of combined radiotherapy and EGFR inhibition with antibodies or TK inhibitors on local tumour control and correlation with EGFR gene expression. Radiother Oncol 2011, 99:323-330.
181. Shin H.K., Kim M-S., Lee J.K., Lee S-S., Ji Y.H., Kim J-I., et al. Combination effect of cetuximab with radiation in colorectal cancer cells. Tumori 2010, 96:713-720.
182. Eke I., Ingargiola M., Förster C., Kunz-Schughart L.A., Baumann M., Runge R., et al. Cytotoxic properties of radionuclide-conjugated Cetuximab without and in combination with external irradiation in head and neck cancer cells in vitro. Int J Radiat Biol 2014, 10.3109/09553002.2014.899446.
183. Rodemann H.P., Dittmann K., Toulany M. Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol 2007, 83:781-791.
184. Dittmann K., Mayer C., Rodemann H-P. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol 2005, 76:157-161.
185. Krause M., Schütze C., Petersen C., Pimentel N., Hessel F., Harstrick A., et al. Different classes of EGFR inhibitors may have different potential to improve local tumour control after fractionated irradiation: a study on C225 in FaDu hSCC. Radiother Oncol 2005, 74:109-115.
186. Bonner J.A., Harari P.M., Giralt J., Cohen R.B., Jones C.U., Sur R.K., et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010, 11:21-28.
187. Ang K., Zhang Q. A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas (HNC). J Clin Oncol 2011 ASCO Annu Meet Abstr 2011 2011, 29:5500.
188. Maughan T.S., Adams R.A., Smith C.G., Meade A.M., Seymour M.T., Wilson R.H., et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011, 377:2103-2114.
189. Philip P.A., Benedetti J., Fenoglio-Preiser C., Zalupski M., Lenz H., O'Reilly E., et al. Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study. J Clin Oncol 2007 ASCO Annu Meet Proc 2007 2007, 25:LBA4509.
190. Lièvre A., Bachet J-B., Le Corre D., Boige V., Landi B., Emile J-F., et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006, 66:3992-3995.
191. Tejpar S., Celik I., Schlichting M., Sartorius U., Bokemeyer C., Van Cutsem E. Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol 2012, 30:3570-3577.
192. Hirsch F.R., Herbst R.S., Olsen C., Chansky K., Crowley J., Kelly K., et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol 2008, 26:3351-3357.
193. Guha U., Chaerkady R., Marimuthu A., Patterson A.S., Kashyap M.K., Harsha H.C., et al. Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS. Proc Natl Acad Sci U S A 2008, 105:14112-14117.
194. Ohashi K., Sequist L.V., Arcila M.E., Moran T., Chmielecki J., Lin Y-L., et al. Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc Natl Acad Sci U S A 2012, 109:E2127-E2133.
195. Diaz L.A., Williams R.T., Wu J., Kinde I., Hecht J.R., Berlin J., et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012, 486:537-540.
196. Moore M.J., Goldstein D., Hamm J., Figer A., Hecht J.R., Gallinger S., et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007, 25:1960-1966.
197. Petrás M., Lajtos T., Friedländer E., Klekner A., Pintye E., Feuerstein B.G., et al. Molecular interactions of ErbB1 (EGFR) and integrin-β1 in astrocytoma frozen sections predict clinical outcome and correlate with Akt-mediated in vitro radioresistance. Neuro Oncol 2013, 15:1027-1040.
198. Moro L., Venturino M., Bozzo C., Silengo L., Altruda F., Beguinot L., et al. Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival. EMBO J 1998, 17:6622-6632.
199. Morello V., Cabodi S., Sigismund S., Camacho-Leal M.P., Repetto D., Volante M., et al. β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells. Oncogene 2011, 30:4087-4096.