Integration of autophagy and anoikis resistance in solid tumors

Anatomical Record

Volumn 296, Issue 10, 2013, Pages 1501-1508

  Yang, Jie ^a   Zheng, Zhichao ^b   Yan, Xiaojie ^a   Li, Xia ^c   Liu, Zhe ^b,d,e,f   Ma, Zhenyi ^a  

^a Department of Biochemistry and Molecular Biology ^*  (China)

^b TIANJIN MEDICAL UNIVERSITY   (China)

^c TIANJIN UNIVERSITY   (China)

^d Tianjin Research Center of Basic Medical Science   (China)

^e Tianjin Key Laboratory of Medical Epigenetics   (China)

^f 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics   (China)

Author keywords

Anoikis; Anoikis resistance; Autophagic cell death; Metastasis; Solid tumor

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 3 METHYLADENINE; ANISOMYCIN; ANTHOCYANIN; ANTINEOPLASTIC AGENT; APIGENIN; BAFILOMYCIN A1; CETUXIMAB; CHLOROQUINE; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; HISTONE DEACETYLASE INHIBITOR; HYDROXYCHLOROQUINE; MONENSIN; N (4 HYDROXYPHENYL) RETINAMIDE; NAVITOCLAX; ORIDONIN; RETINOID; SORAFENIB; TRICHOSTATIN A; UNCLASSIFIED DRUG; VORINOSTAT; WORTAMANNIN; WZ 4002;

ANOIKIS; ANTINEOPLASTIC ACTIVITY; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CANCER CELL; CANCER THERAPY; CELL DEATH; CELL SURVIVAL; HUMAN; INTRACELLULAR SIGNALING; METASTASIS; NONHUMAN; PRIORITY JOURNAL; SOLID TUMOR;

ANOIKIS; ANOIKIS RESISTANCE; AUTOPHAGIC CELL DEATH; METASTASIS; SOLID TUMOR;

ANIMALS; ANOIKIS; AUTOPHAGY; CELL COMMUNICATION; HUMANS; NEOPLASMS;

EID: 84884279893     PISSN: 19328486     EISSN: 19328494     Source Type: Journal    
DOI: 10.1002/ar.22769     Document Type: Article

References (96)

1. Attwell S, Roskelley C, Dedhar S. 2000. The integrin-linked kinase (ILK) suppresses anoikis. Oncogene 19:3811-3815.
2. Avivar-Valderas A, Salas E, Bobrovnikova-Marjon E, Diehl JA, Nagi C, Debnath J, Aguirre-Ghiso JA. 2011. PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment. Mol Cell Biol 31:3616-3629.
3. Banerjee P, Basu A, Wegiel B, Otterbein LE, Mizumura K, Gasser M, Waaga-Gasser AM, Choi AM, Pal S. 2012. Heme oxygenase-1 promotes survival of renal cancer cells through modulation of apoptosis- and autophagy-regulating molecules. J Biol Chem 287:32113-32123.
4. Becker-Santos DD, Guo Y, Ghaffari M, Vickers ED, Lehman M, Altamirano-Dimas M, Oloumi A, Furukawa J, Sharma M, Wang Y, Dedhar S, Cox ME. 2012. Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models. Carcinogenesis 33:2558-2567.
5. Bergmann A. 2007. Autophagy and cell death: no longer at odds. Cell 131:1032-1034.
6. Broustas CG, Zhu A, Lieberman HB. 2012. Rad9 protein contributes to prostate tumor progression by promoting cell migration and anoikis resistance. J Biol Chem 287:41324-41333.
7. Chang Y, Chen L, Liu Y, Hu L, Li L, Tu Q, Wang R, Wu M, Yang J, Wang H. 2011. Inhibition of autophagy may suppress the development of hepatoblastoma. FEBS J 278:4811-4823.
8. Chen LH, Loong CC, Su TL, Lee YJ, Chu PM, Tsai ML, Tsai PH, Tu PH, Chi CW, Lee HC, Chiou SH. 2011. Autophagy inhibition enhances apoptosis triggered by BO-1051, an N-mustard derivative, and involves the ATM signaling pathway. Biochem Pharmacol 81:594-605.
9. Chen N, Eritja N, Lock R, Debnath J. 2012. Autophagy restricts proliferation driven by oncogenic phosphatidylinositol 3-kinase in three-dimensional culture. Oncogene. DOI: 10.1038/onc.2012.277.
10. Chen N, Karantza-Wadsworth V. 2009. Role and regulation of autophagy in cancer. Biochim Biophys Acta 1793:1516-1523.
11. Chen Y, Azad MB, Gibson SB. 2009. Superoxide is the major reactive oxygen species regulating autophagy. Cell Death Differ 16:1040-1052.
12. Cheng H, Liu P, Wang ZC, Zou L, Santiago S, Garbitt V, Gjoerup OV, Iglehart JD, Miron A, Richardson AL, Hahn WC, Zhao JJ. 2009. SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis. Sci Signal 2:ra35.
13. Debnath J. 2008. Detachment-induced autophagy during anoikis and lumen formation in epithelial acini. Autophagy 4:351-353.
14. Denton D, Chang TK, Nicolson S, Shravage B, Simin R, Baehrecke EH, Kumar S. 2012. Relationship between growth arrest and autophagy in midgut programmed cell death in Drosophila. Cell Death Differ 19:1299-1307.
15. Douma S, Van Laar T, Zevenhoven J, Meuwissen R, Van Garderen E, Peeper DS. 2004. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 430:1034-1039.
16. Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE. 2004. Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells. Surgery 135:555-562.
17. El-Naggar S, Liu Y, Dean DC. 2009. Mutation of the Rb1 pathway leads to overexpression of mTor, constitutive phosphorylation of Akt on serine 473, resistance to anoikis, and a block in c-Raf activation. Mol Cell Biol 29:5710-5717.
18. Elgendy M, Sheridan C, Brumatti G, Martin SJ. 2011. Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival. Mol Cell 42:23-35.
19. Frisch SM, Francis H. 1994. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619-626.
20. Frisch SM, Ruoslahti E. 1997. Integrins and anoikis. Curr Opin Cell Biol 9:701-706.
21. Fung C, Lock R, Gao S, Salas E, Debnath J. 2008. Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol Biol Cell 19:797-806.
22. Gammoh N, Marks PA, Jiang X. 2012. Curbing autophagy and histone deacetylases to kill cancer cells. Autophagy 8:1521-1522.
23. Gan B, Yoo Y, Guan JL. 2006. Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth. J Biol Chem 281:37321-37329.
24. Gassmann P, Haier J. 2008. The tumor cell-host organ interface in the early onset of metastatic organ colonisation. Clin Exp Metastasis 25:171-181.
25. Gewirtz DA. 2009. Autophagy, senescence and tumor dormancy in cancer therapy. Autophagy 5:1232-1234.
26. Ghosh A, Chen TC, Kapila YL. 2010. Anoikis triggers Mdm2-dependent p53 degradation. Mol Cell Biochem 343:201-209.
27. Giannoni E, Buricchi F, Grimaldi G, Parri M, Cialdai F, Taddei ML, Raugei G, Ramponi G, Chiarugi P. 2008. Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival. Cell Death Differ 15:867-878.
28. Gonzalez P, Mader I, Tchoghandjian A, Enzenmuller S, Cristofanon S, Basit F, Debatin KM, Fulda S. 2012. Impairment of lysosomal integrity by B10, a glycosylated derivative of betulinic acid, leads to lysosomal cell death and converts autophagy into a detrimental process. Cell Death Differ 19:1337-1346.
29. Guadamillas MC, Cerezo A, Del Pozo MA. 2011. Overcoming anoikis-pathways to anchorage-independent growth in cancer. J Cell Sci 124:3189-3197.
30. Hausmann M, Leucht K, Ploner C, Kiessling S, Villunger A, Becker H, Hofmann C, Falk W, Krebs M, Kellermeier S, Fried M, Scholmerich J, Obermeier F, Rogler G. 2011. BCL-2 modifying factor (BMF) is a central regulator of anoikis in human intestinal epithelial cells. J Biol Chem 286:26533-26540.
31. Horbinski C, Mojesky C, Kyprianou N. 2010. Live free or die: tales of homeless (cells) in cancer. Am J Pathol 177:1044-1052.
32. Hu YL, DeLay M, Jahangiri A, Molinaro AM, Rose SD, Carbonell WS, Aghi MK. 2012a. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. Cancer Res 72:1773-1783.
33. Hu YL, Jahangiri A, Delay M, Aghi MK. 2012b. Tumor cell autophagy as an adaptive response mediating resistance to treatments such as antiangiogenic therapy. Cancer Res 72:4294-4299.
34. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Janne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK. 2007. LKB1 modulates lung cancer differentiation and metastasis. Nature 448:807-810.
35. Jiang H, Martin V, Gomez-Manzano C, Johnson DG, Alonso M, White E, Xu J, McDonnell TJ, Shinojima N, Fueyo J. 2010. The RB-E2F1 pathway regulates autophagy. Cancer Res 70:7882-7893.
36. Jung KH, Noh JH, Kim JK, Eun JW, Bae HJ, Chang YG, Kim MG, Park WS, Lee JY, Lee SY, Chu IS, Nam SW. 2012. Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer. Hepatology 56:644-657.
37. Kenific CM, Thorburn A, Debnath J. 2010. Autophagy and metastasis: another double-edged sword. Curr Opin Cell Biol 22:241-245.
38. Kim YN, Koo KH, Sung JY, Yun UJ, Kim H. 2012. Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol 2012:306879.
39. Kondo K, Makita T. 1997. Inhibition of peroxisomal degradation by 3-methyladenine (3MA) in primary cultures of rat hepatocytes. Anat Rec 247:449-454.
40. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H, Ogawa S, Kaufman RJ, Kominami E, Momoi T. 2007. ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ 14:230-239.
41. Kumar S, Park SH, Cieply B, Schupp J, Killiam E, Zhang F, Rimm DL, Frisch SM. 2011. A pathway for the control of anoikis sensitivity by E-cadherin and epithelial-to-mesenchymal transition. Mol Cell Biol 31:4036-4051.
42. Lee IH, Kawai Y, Fergusson MM, Rovira, II, Bishop AJ, Motoyama N, Cao L, Finkel T. 2012. Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science 336:225-228.
43. Levine B. 2006. Unraveling the role of autophagy in cancer. Autophagy 2:65-66.
44. Levine B. 2007. Cell biology: autophagy and cancer. Nature 446:745-747.
45. Li X, Fan Z. 2010. The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex. Cancer Res 70:5942-5952.
46. Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, Wang ZC, Richardson AL. 2011. Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer Res 71:7481-7489.
47. Liang C, Jung JU. 2010. Autophagy genes as tumor suppressors. Curr Opin Cell Biol 22:226-233.
48. Liu YL, Yang PM, Shun CT, Wu MS, Weng JR, Chen CC. 2010. Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma. Autophagy 6:1057-1065.
49. Liu Z, Li H, Derouet M, Filmus J, LaCasse EC, Korneluk RG, Kerbel RS, Rosen KV. 2005. ras Oncogene triggers up-regulation of cIAP2 and XIAP in intestinal epithelial cells: epidermal growth factor receptor-dependent and -independent mechanisms of ras-induced transformation. J Biol Chem 280:37383-37392.
50. Lock R, Debnath J. 2008. Extracellular matrix regulation of autophagy. Curr Opin Cell Biol 20:583-588.
51. Lock R, Roy S, Kenific CM, Su JS, Salas E, Ronen SM, Debnath J. 2011. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell 22:165-178.
52. Longo L, Platini F, Scardino A, Alabiso O, Vasapollo G, Tessitore L. 2008. Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma. Mol Cancer Ther 7:2476-2485.
53. Lu Z, Luo RZ, Lu Y, Zhang X, Yu Q, Khare S, Kondo S, Kondo Y, Yu Y, Mills GB, Liao WS, Bast RC, Jr. 2008. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J Clin Invest 118:3917-3929.
54. Shc restrains Ras hyperactivation and suppresses metastatic behavior. Oncogene 29:5559-5567.
55. Ma Z, Myers DP, Wu RF, Nwariaku FE, Terada LS. 2007. p66Shc mediates anoikis through RhoA. J Cell Biol 179:23-31.
56. Mathew R, White E. 2011. Autophagy, stress, and cancer metabolism: what doesn't kill you makes you stronger. Cold Spring Harb Symp Quant Biol 76:389-396.
57. Mawji IA, Simpson CD, Gronda M, Williams MA, Hurren R, Henderson CJ, Datti A, Wrana JL, Schimmer AD. 2007. A chemical screen identifies anisomycin as an anoikis sensitizer that functions by decreasing FLIP protein synthesis. Cancer Res 67:8307-8315.
58. McFall A, Ulku A, Lambert QT, Kusa A, Rogers-Graham K, Der CJ. 2001. Oncogenic Ras blocks anoikis by activation of a novel effector pathway independent of phosphatidylinositol 3-kinase. Mol Cell Biol 21:5488-5499.
59. Mohan N, Banik NL, Ray SK. 2011. Combination of N-(4-hydroxyphenyl) retinamide and apigenin suppressed starvation-induced autophagy and promoted apoptosis in malignant neuroblastoma cells. Neurosci Lett 502:24-29.
60. Moro L, Arbini AA, Yao JL, di Sant'Agnese PA, Marra E, Greco M. 2009. Mitochondrial DNA depletion in prostate epithelial cells promotes anoikis resistance and invasion through activation of PI3K/Akt2. Cell Death Differ 16:571-583.
61. Oh M, Choi IK, Kwon HJ. 2008. Inhibition of histone deacetylase1 induces autophagy. Biochem Biophys Res Commun 369:1179-1183.
62. Parsons MJ, Patel P, Brat DJ, Colbert L, Vertino PM. 2009. Silencing of TMS1/ASC promotes resistance to anoikis in breast epithelial cells. Cancer Res 69:1706-1711.
63. Penna E, Orso F, Cimino D, Tenaglia E, Lembo A, Quaglino E, Poliseno L, Haimovic A, Osella-Abate S, De Pitta C, Pinatel E, Stadler MB, Provero P, Bernengo MG, Osman I, Taverna D. 2011. microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C. EMBO J 30:1990-2007.
64. Pongrakhananon V, Nimmannit U, Luanpitpong S, Rojanasakul Y, Chanvorachote P. 2010. Curcumin sensitizes non-small cell lung cancer cell anoikis through reactive oxygen species-mediated Bcl-2 downregulation. Apoptosis 15:574-585.
65. Pyo JO, Nah J, Jung YK. 2012. Molecules and their functions in autophagy. Exp Mol Med 44:73-80.
66. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, Cattoretti G, Levine B. 2003. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 112:1809-1820.
67. Ravid D, Maor S, Werner H, Liscovitch M. 2005. Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling. Oncogene 24:1338-1347.
68. Reginato MJ, Mills KR, Paulus JK, Lynch DK, Sgroi DC, Debnath J, Muthuswamy SK, Brugge JS. 2003. Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol 5:733-740.
69. Rosen K, Rak J, Jin J, Kerbel RS, Newman MJ, Filmus J. 1998. Downregulation of the pro-apoptotic protein Bak is required for the ras-induced transformation of intestinal epithelial cells. Curr Biol 8:1331-1334.
70. Rosen K, Rak J, Leung T, Dean NM, Kerbel RS, Filmus J. 2000. Activated Ras prevents downregulation of Bcl-X(L) triggered by detachment from the extracellular matrix. A mechanism of Ras-induced resistance to anoikis in intestinal epithelial cells. J Cell Biol 149:447-456.
71. Sakuma Y, Yamazaki Y, Nakamura Y, Yoshihara M, Matsukuma S, Nakayama H, Yokose T, Kameda Y, Koizume S, Miyagi Y. 2012. WZ4002, a third-generation EGFR inhibitor, can overcome anoikis resistance in EGFR-mutant lung adenocarcinomas more efficiently than Src inhibitors. Lab Invest 92:371-383.
72. Shang L, Chen S, Du F, Li S, Zhao L, Wang X. 2011. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci USA 108:4788-4793.
73. Shen HM, Codogno P. 2011. Autophagic cell death: Loch Ness monster or endangered species? Autophagy 7:457-465.
74. Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, Tsujimoto Y. 2004. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6:1221-1228.
75. Shimizu S, Takehara T, Hikita H, Kodama T, Tsunematsu H, Miyagi T, Hosui A, Ishida H, Tatsumi T, Kanto T, Hiramatsu N, Fujita N, Yoshimori T, Hayashi N. 2012. Inhibition of autophagy potentiates the antitumor effect of the multikinase inhibitor sorafenib in hepatocellular carcinoma. Int J Cancer 131:548-557.
76. Smit MA, Geiger TR, Song JY, Gitelman I, Peeper DS. 2009. A Twist-Snail axis critical for TrkB-induced epithelial-mesenchymal transition-like transformation, anoikis resistance, and metastasis. Mol Cell Biol 29:3722-3737.
77. Smit MA, Peeper DS. 2011. Zeb1 is required for TrkB-induced epithelial-mesenchymal transition, anoikis resistance and metastasis. Oncogene 30:3735-3744.
78. Szatrowski TP, Nathan CF. 1991. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 51:794-798.
79. Taddei ML, Giannoni E, Fiaschi T, Chiarugi P. 2012. Anoikis: an emerging hallmark in health and diseases. J Pathol 226:380-393.
80. Tolkovsky AM. 2009. Mitophagy. Biochim Biophys Acta 1793:1508-1515.
81. Tsuchihara K, Fujii S, Esumi H. 2009. Autophagy and cancer: dynamism of the metabolism of tumor cells and tissues. Cancer Lett 278:130-138.
82. Verschooten L, Barrette K, Van Kelst S, Rubio Romero N, Proby C, De Vos R, Agostinis P, Garmyn M. 2012. Autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells. PLoS ONE 7:e48264.
83. Vigil D, Kim TY, Plachco A, Garton AJ, Castaldo L, Pachter JA, Dong H, Chen X, Tokar B, Campbell SL, Der CJ. 2012. ROCK1 and ROCK2 are required for non-small cell lung cancer anchorage-independent growth and invasion. Cancer Res 72:5338-5347.
84. Wang P, Valentijn AJ, Gilmore AP, Streuli CH. 2003. Early events in the anoikis program occur in the absence of caspase activation. J Biol Chem 278:19917-19925.
85. Wang RC, Wei Y, An Z, Zou Z, Xiao G, Bhagat G, White M, Reichelt J, Levine B. 2012. Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science 338:956-959.
86. Wirawan E, Vanden Berghe T, Lippens S, Agostinis P, Vandenabeele P. 2012. Autophagy: for better or for worse. Cell Res 22:43-61.
87. Xia H, Nho RS, Kahm J, Kleidon J, Henke CA. 2004. Focal adhesion kinase is upstream of phosphatidylinositol 3-kinase/Akt in regulating fibroblast survival in response to contraction of type I collagen matrices via a beta 1 integrin viability signaling pathway. J Biol Chem 279:33024-33034.
88. Yang ZJ, Chee CE, Huang S, Sinicrope FA. 2011. The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther 10:1533-1541.
89. Ye LH, Li WJ, Jiang XQ, Chen YL, Tao SX, Qian WL, He JS. 2012. Study on the autophagy of prostate cancer PC-3 cells induced by oridonin. Anat Rec (Hoboken) 295:417-422.
90. Yoo BH, Wu X, Li Y, Haniff M, Sasazuki T, Shirasawa S, Eskelinen EL, Rosen KV. 2010. Oncogenic ras-induced down-regulation of autophagy mediator Beclin-1 is required for malignant transformation of intestinal epithelial cells. J Biol Chem 285:5438-5449.
91. Yu L, Wan F, Dutta S, Welsh S, Liu Z, Freundt E, Baehrecke EH, Lenardo M. 2006. Autophagic programmed cell death by selective catalase degradation. Proc Natl Acad Sci USA 103:4952-4957.
92. Yu X, Liu L, Cai B, He Y, Wan X. 2008. Suppression of anoikis by the neurotrophic receptor TrkB in human ovarian cancer. Cancer Sci 99:543-552.
93. Zhao Y, Xiong X, Sun Y. 2011. DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(betaTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Mol Cell 44:304-316.
94. Zheng Y, Gierut J, Wang Z, Miao J, Asara JM, Tyner AL. 2012. Protein tyrosine kinase 6 protects cells from anoikis by directly phosphorylating focal adhesion kinase and activating AKT. Oncogene. DOI: 10.1038/onc.2012.427.
95. Zou CF, Jia L, Jin H, Yao M, Zhao N, Huan J, Lu Z, Bast RC, Jr., Feng Y, Yu Y. 2011. Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel. BMC Cancer 11:22.
96. Zugasti O, Rul W, Roux P, Peyssonnaux C, Eychene A, Franke TF, Fort P, Hibner U. 2001. Raf-MEK-Erk cascade in anoikis is controlled by Rac1 and Cdc42 via Akt. Mol Cell Biol 21:6706-6717.