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Journal of Cancer Research and Clinical Oncology

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01-11-2013 | Review

Uncovering a key to the process of metastasis in human cancers: a review of critical regulators of anoikis

Authors: Kevin Tan, David Goldstein, Philip Crowe, Jia-Lin Yang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2013

Abstract

Purpose

Anoikis (‘homelessness’ in Greek) is a form of apoptosis following the detachment of cells from the appropriate extracellular matrix (Chiarugi and Giannoni in Biochem Pharmacol 76:1352–1364, 2008). Resistance to anoikis is a critical mediator of metastasis in cancer by enabling cancer cells to survive during invasion and transport in the blood and lymph. Numerous regulators and mechanisms of anoikis in human cancer have been proposed to date. Consequently, the identification of key regulators of anoikis that can be targeted to at least partially restore anoikis sensitivity in cancer cells is important in the development of therapies to treat metastatic cancer.

Methods

A literature search focusing on the regulators of anoikis in human cancer was performed on the Medline, Embase and Scopus databases.

Results

Mcl-1, Cav-1, Bcl-x_L, cFLIP, 14-3-3ζ and Bit1 appear to regulate anoikis in human cancer by participating in the intrinsic apoptotic pathway, extrinsic apoptotic pathway or caspase-independent pathways. Mcl-1, Cav-1, Bcl-x_L, cFLIP and 14-3-3ζ are suppressors of anoikis, and their upregulation confers anoikis resistance to cancer cells. Bit1 is a promoter of anoikis and is downregulated to confer anoikis resistance in metastatic cancer.

Conclusion

Anoikis is a complex process involving the crosstalk between different signalling pathways. The dysregulated expression of key regulators of anoikis that participate in these signalling pathways promotes anoikis resistance in human cancer. These regulators of anoikis might therefore be the targets for developing therapies to overcome anoikis resistance in metastatic cancer.

Adams JM, Cory S (2007) The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26(9):1324–1337. doi:10.1038/sj.onc.1210220 PubMedCrossRef

Akiyama T, Dass CR, Choong PFM (2009) Bim-targeted cancer therapy: a link between drug action and underlying molecular changes. Mol Cancer Ther 8(12):3173–3180. doi:10.1158/1535-7163.MCT-09-0685 PubMedCrossRef

Alfano D, Iaccarino I, Stoppelli MP (2006) Urokinase signaling through its receptor protects against anoikis by increasing BCL-xL expression levels. J Biol Chem 281(26):17758–17767PubMedCrossRef

Bagnoli M, Canevari S, Mezzanzanica D (2010) Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer. Int J Biochem Cell Biol 42(2):210–213. doi:10.1016/j.biocel.2009.11.015 PubMedCrossRef

Beagle B, Johnson GV (2010) AES/GRG5: more than just a dominant-negative TLE/GRG family member. Dev Dyn 239(11):2795–2805. doi:10.1002/dvdy.22439 PubMedCrossRef

Biliran H, Jan Y, Chen R, Pasquale EB, Ruoslahti E (2008) Protein kinase D is a positive regulator of Bit1 apoptotic function. J Biol Chem 283(42):28029–28037. doi:10.1074/jbc.M803139200 PubMedCrossRef

Boisvert-Adamo K, Longmate W, Abel EV, Aplin AE (2009) Mcl-1 is required for melanoma cell resistance to anoikis. Mol Cancer Res 7(4):549–556. doi:10.1158/1541-7786.MCR-08-0358 PubMedCrossRef

Bridges D, Moorhead GB (2005) 14-3-3 proteins: a number of functions for a numbered protein. Science’s STKE (electronic resource): signal transduction knowledge environment (296)

Brunquell C, Biliran H, Jennings S, Ireland SK, Chen R, Ruoslahti E (2012) TLE1 is an anoikis regulator and is downregulated by Bit1 in breast cancer cells. Mol Cancer Res 10(11):1482–1495. doi:10.1158/1541-7786.MCR-12-0144 PubMedCrossRef

Chaabane W, User SD, El-Gazzah M, Jaksik R, Sajjadi E, Rzeszowska-Wolny J, Łos MJ (2013) Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp 61(1):43–58CrossRef

Chen HX, Liu YJ, Zhou XD, Luo RY (2005) Expression of cellular FLICE/caspase-8 inhibitory protein is associated with malignant potential in endometrial carcinoma. Int J Gynecol Cancer 15(4):663–670PubMedCrossRef

Chen LC, Chung IC, Hsueh C, Tsang NM, Chi LM, Liang Y, Chen CC, Wang LJ, Chang YS (2010) The antiapoptotic protein, FLIP, is regulated by heterogeneous nuclear ribonucleoprotein K and correlates with poor overall survival of nasopharyngeal carcinoma patients. Cell Death Differ 17(9):1463–1473PubMedCrossRef

Chen C, Zhou H, Wei F, Jiang L, Liu X, Liu Z, Ma Q (2011) Increased levels of hypoxia-inducible factor-1α are associated with Bcl-xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma. J Orthop Res 29(1):143–151PubMedCrossRef

Chen R, Braun GB, Luo X, Sugahara KN, Teesalu T, Ruoslahti E (2013) Application of a proapoptotic peptide to intratumorally spreading cancer therapy. Cancer Res 73(4):1352–1361. doi:10.1158/0008-5472.CAN-12-1979 PubMedCrossRef

Chiarugi P, Giannoni E (2008) Anoikis: a necessary death program for anchorage-dependent cells. Biochem Pharmacol 76(11):1352–1364. doi:10.1016/j.bcp.2008.07.023 PubMedCrossRef

Chunhacha P, Pongrakhananon V, Rojanasakul Y, Chanvorachote P (2012) Caveolin-1 regulates Mcl-1 stability and anoikis in lung carcinoma cells. Am J Physiol Cell Physiol 302(9):C1284–C1292. doi:10.1152/ajpcell.00318.2011 PubMedCrossRef

Coates JM, Galante JM, Bold RJ (2010) Cancer therapy beyond apoptosis: autophagy and anoikis as mechanisms of cell death. J Surg Res 164(2):301–308PubMedCrossRef

Coll ML, Rosen K, Ladeda V, Filmus J (2002) Increased Bcl-xL expression mediates v-Src-induced resistance to anoikis in intestinal epithelial cells. Oncogene 21(18):2908–2913PubMedCrossRef

Daisy P, Saipriya K (2012) BCL-2 family proteins: the mitochondrial apoptotic key regulators. Curr Cancer Ther Rev 8(2):133–140CrossRef

Danes CG, Wyszomierski SL, Lu J, Neal CL, Yang W, Yu D (2008) 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal filling. Cancer Res 68(6):1760–1767. doi:10.1158/0008-5472.CAN-07-3177 PubMedCrossRef

Danial NN (2007) BCL-2 family proteins: critical checkpoints of apoptotic cell death. Clin Cancer Res 13(24):7254–7263. doi:10.1158/1078-0432.CCR-07-1598 PubMedCrossRef

Ekert PG, Vaux DL (2005) The mitochondrial death squad: hardened killers or innocent bystanders? Curr Opin Cell Biol 17(6):626–630. doi:10.1016/j.ceb.2005.09.001 PubMedCrossRef

Fan YJ, Zong WX (2013) The cellular decision between apoptosis and autophagy. Chin J Cancer 32(3):121–129PubMed

Fan T, Li R, Todd NW, Qiu Q, Fang HB, Wang H, Shen J, Zhao RY, Caraway NP, Katz RL, Stass SA, Jiang F (2007) Up-regulation of 14-3-3ζ in lung cancer and its implication as prognostic and therapeutic target. Cancer Res 67(16):7901–7906PubMedCrossRef

Fan Y, Zhang YL, Wu Y, Zhang W, Wang YH, Cheng ZM, Li H (2008) Inhibition of signal transducer and activator of transcription 3 expression by RNA interference suppresses invasion through inducing anoikis in human colon cancer cells. World J Gastroenterol 14(3):428–434PubMedCrossRef

Fleischer B, Schulze-Bergkamen H, Schuchmann M, Weber A, Biesterfeld S, Müller M, Krammer PH, Galle PR (2006) Mcl-1 is an anti-apoptotic factor for human hepatocellular carcinoma. Int J Oncol 28(1):25–32PubMed

Frankel A, Rosen K, Filmus J, Kerbel RS (2001) Induction of anoikis and suppression of human ovarian tumor growth in vivo by down-regulation of Bcl-X(L). Cancer Res 61(12):4837–4841PubMed

Fridman JS, Lowe SW (2003) Control of apoptosis by p53. Oncogene 22(56 REV. ISS. 8):9030–9040

Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13(5):555–562. doi:10.1016/S0955-0674(00)00251-9 PubMedCrossRef

Fu H, Subramanian RR, Masters SC (2000) 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647

Gasperowicz M, Otto F (2005) Mammalian Groucho homologs: redundancy or specificity? J Cell Biochem 95(4):670–687. doi:10.1002/jcb.20476 PubMedCrossRef

Geiger TR, Peeper DS (2009) Metastasis mechanisms. Biochim Biophys Acta Rev Cancer 1796(2):293–308CrossRef

Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281(5381):1309–1312PubMedCrossRef

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedCrossRef

Hermeking H, Benzinger A (2006) 14-3-3 proteins in cell cycle regulation. Semin Cancer Biol 16(3):183–192. doi:10.1016/j.semcancer.2006.03.002 PubMedCrossRef

Jan Y, Matter M, Pai JT, Chen YL, Pilch J, Komatsu M, Ong E, Fukuda M, Ruoslahti E (2004) A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Cell 116(5):751–762. doi:10.1016/S0092-8674(04)00204-1 PubMedCrossRef

Jenning S, Pham T, Ireland SK, Ruoslahti E, Biliran H (2013) Bit1 in anoikis resistance and tumor metastasis. Cancer Lett. doi:10.1016/j.canlet.2013.01.043 PubMed

Jensen K, Patel A, Klubo-Gwiezdzinska J, Bauer A, Vasko V (2011) Inhibition of gap junction transfer sensitizes thyroid cancer cells to anoikis. Endocr Relat Cancer 18(5):613–626PubMedCrossRef

Jin Z, El-Deiry WS (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4(2):139–163PubMedCrossRef

Jin-Song Y, Zhao-Xia W, Cheng-Yu L, Xiao-Di L, Ming S, Yuan–Yuan G, Wei D (2011) Prognostic significance of Bcl-xL gene expression in human colorectal cancer. Acta Histochem 113(8):810–814PubMedCrossRef

Kairouz-Wahbe R, Biliran H, Luo X, Khor I, Wankell M, Besch-Williford C, Pascual J, Oshima R, Ruoslahti E (2008) Anoikis effector Bit1 negatively regulates Erk activity. Proc Natl Acad Sci USA 105(5):1528–1532. doi:10.1073/pnas.0711357105 PubMedCrossRef

Kanayama S, Yamada Y, Kawaguchi R, Tsuji Y, Haruta S, Kobayashi H (2008) Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells. Oncol Rep 19(1):117–122PubMed

Karmali PP, Brunquell C, Tram H, Ireland SK, Ruoslahti E, Biliran H (2011) Metastasis of tumor cells is enhanced by downregulation of Bit1. PLoS One 6(8):e23840. doi:10.1371/journal.pone.0023840 PubMedCrossRef

Kim YN, Koo KH, Sung JY, Yun UJ, Kim H (2012) Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol 2012. Article ID 306879. doi:10.1155/2012/306879

Li Z, Zhao J, Du Y, Park HR, Sun SY, Bernal-Mizrachi L, Aitken A, Khuri FR, Fu H (2008) Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci USA 105(1):162–167PubMedCrossRef

Liu K, Liu F, Zhang N, Liu S, Jiang Y (2012) Pokemon silencing leads to bim-mediated anoikis of human hepatoma cell QGY7703. Int J Mol Sci 13(5):5818–5831. doi:10.3390/ijms13055818 PubMedCrossRef

Lovell JF, Billen LP, Bindner S, Shamas-Din A, Fradin C, Leber B, Andrews DW (2008) Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by bax. Cell 135(6):1074–1084. doi:10.1016/j.cell.2008.11.010 PubMedCrossRef

Matta A, Michael Siu KW, Ralhan R (2012) 14-3-3 zeta as novel molecular target for cancer therapy. Expert Opin Ther Targets 16(5):515–523CrossRef

Mawji IA, Simpson CD, Hurren R, Gronda M, Williams MA, Filmus J, Jonkman J, Da Costa RS, Wilson BC, Thomas MP, Reed JC, Glinsky GV, Schimmer AD (2007) Critical role for fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein in anoikis resistance and distant tumor formation. J Natl Cancer Inst 99(10):811–822PubMedCrossRef

Michels J, Johnson PWM, Packham G (2005) Mcl-1. Int J Biochem Cell Biol 37(2):267–271. doi:10.1016/j.biocel.2004.04.007 PubMedCrossRef

Neal CL, Yu D (2010) 14-3-3ζ as a prognostic marker and therapeutic target for cancer. Expert Opin Ther Targets 14(12):1343–1354. doi:10.1517/14728222.2010.531011 PubMedCrossRef

Neal CL, Yao J, Yang W, Zhou X, Nguyen NT, Lu J, Danes CG, Guo H, Lan KH, Ensor J, Hittelman W, Hung MC, Yu D (2009) 14-3-3ζ overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival. Cancer Res 69(8):3425–3432. doi:10.1158/0008-5472.CAN-08-2765 PubMedCrossRef

Nelson CM, Bissell MJ (2006) Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu Rev Cell Dev Biol 22:287–309

Ng YK, Wong EYL, Lau CPY, Chan JPL, Wong SCC, Chan ASK, Kwan MPC, Tsao SW, Tsang CM, Lai PBS, Chan ATC, Lui VWY (2012) K252a induces anoikis-sensitization with suppression of cellular migration in Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma cells. Invest New Drugs 30(1):48–58PubMedCrossRef

Obsil T, Obsilova V (2011) Structural basis of 14-3-3 protein functions. Semin Cell Dev Biol 22(7):663–672. doi:10.1016/j.semcdb.2011.09.001 PubMedCrossRef

Ott M, Norberg E, Zhivotovsky B, Orrenius S (2009) Mitochondrial targeting of tBid/Bax: a role for the TOM complex? Cell Death Differ 16(8):1075–1082PubMedCrossRef

Pepper C, Lin TT, Pratt G, Hewamana S, Brennan P, Hiller L, Hills R, Ward R, Starczynski J, Austen B, Hooper L, Stankovic T, Fegan C (2008) Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood 112(9):3807–3817PubMedCrossRef

Rao-Bindal K, Rao CK, Yu L, Kleinerman ES (2013) Expression of c-FLIP in pulmonary metastases in osteosarcoma patients and human xenografts. Pediatr Blood Cancer 60(4):575–579PubMedCrossRef

Ravid D, Maor S, Werner H, Liscovitch M (2006) Caveolin-1 inhibits anoikis and promotes survival signaling in cancer cells. Adv Enzyme Regul 46:163–175

Roucou X, Montessuit S, Antonsson B, Martinou JC (2002) Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein. Biochem J 368(3):915–921. doi:10.1042/BJ20020972 PubMedCrossRef

Safa AR, Pollok KE (2011) Targeting the anti-apoptotic protein c-FLIP for cancer therapy. Cancers 3(2):1639–1671. doi:10.3390/cancers3021639 PubMedCrossRef

Sáinz-Jaspeado M, Martin-Liberal J, Lagares-Tena L, Mateo-Lozano S, del Muro XG, Tirado OM (2011) Caveolin-1 in sarcomas: friend or foe? Oncotarget 2(4):305–312PubMed

Sakamoto S, Kyprianou N (2010) Targeting anoikis resistance in prostate cancer metastasis. Mol Aspects Med 31(2):205–214PubMedCrossRef

Sakuma Y, Tsunezumi J, Nakamura Y, Yoshihara M, Matsukuma S, Koizume S, Miyagi Y (2011) ABT-263, a Bcl-2 inhibitor, enhances the susceptibility of lung adenocarcinoma cells treated with Src inhibitors to anoikis. Oncol Rep 25(3):661–667. doi:10.3892/or.2010.1123 PubMedCrossRef

Sayers TJ (2011) Targeting the extrinsic apoptosis signaling pathway for cancer therapy. Cancer Immunol Immunother 60(8):1173–1180PubMedCrossRef

Seo SW, Lee H, Lee HI, Kim HS (2011) The role of TLE1 in synovial sarcoma. J Orthop Res 29(7):1131–1136. doi:10.1002/jor.21318 PubMedCrossRef

Shigemasa K, Katoh O, Shiroyama Y, Mihara S, Mukai K, Nagai N, Ohama K (2002) Increased MCL-1 expression is associated with poor prognosis in ovarian carcinomas. Jpn J Cancer Res 93(5):542–550PubMedCrossRef

Shirane M, Nakayama KI (2003) Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis. Nat Cell Biol 5(1):28–37. doi:10.1038/ncb894 PubMedCrossRef

Simpson CD, Anyiwe K, Schimmer AD (2008) Anoikis resistance and tumor metastasis. Cancer Lett 272(2):177–185. doi:10.1016/j.canlet.2008.05.029 PubMedCrossRef

Soltani-Arabshahi R, Leboeuf C, Rivet J, Pisonero H, Zhao WL, Bachelez H, Ameisen JC, Janin A (2009) Bcl-xL gene expression correlated with lower apoptotic cell numbers and shorter progression-free survival in PCFCL. J Investig Dermatol 129(7):1703–1709PubMedCrossRef

Stupack DG, Cheresh DA (2004) A Bit-role for integrins in apoptosis. Nat Cell Biol 6(5):388–389. doi:10.1038/ncb0504-388 PubMedCrossRef

Taddei ML, Giannoni E, Fiaschi T, Chiarugi P (2012) Anoikis: an emerging hallmark in health and diseases. J Pathol 226(2):380–393. doi:10.1002/path.3000 PubMedCrossRef

Tan MJ, Teo Z, Sng MK, Zhu P, Tan NS (2012) Emerging roles of angiopoietin-like 4 in human cancer. Mol Cancer Res 10(6):677–688. doi:10.1158/1541-7786.MCR-11-0519 PubMedCrossRef

Tang MKS, Zhou HY, Yam JWP, Wong AST (2010) c-Met overexpression contributes to the acquired apoptotic resistance of nonadherent ovarian cancer cells through a cross talk mediated by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2. Neoplasia 12(2):128–138PubMed

Touzeau C, Dousset C, Bodet L, Gomez-Bougie P, Bonnaud S, Moreau A, Moreau P, Pellat-Deceunynk C, Amiot M, Le Gouill S (2011) ABT-737 induces apoptosis in mantle cell lymphoma cells with a Bcl-2 high/Mcl-1 low profile and synergizes with other antineoplastic agents. Clin Cancer Res 17(18):5973–5981PubMedCrossRef

Uekita T, Sakai R (2011) Roles of CUB domain-containing protein 1 signaling in cancer invasion and metastasis. Cancer Sci 102(11):1943–1948. doi:10.1111/j.1349-7006.2011.02052.x PubMedCrossRef

Uekita T, Jia L, Narisawa-Saito M, Yokota J, Kiyono T, Sakai R (2007) CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma. Mol Cell Biol 27(21):7649–7660PubMedCrossRef

Ullenhag GJ, Mukherjee A, Watson NFS, Al-Attar AH, Scholefield JH, Durrant LG (2007) Overexpression of FLIPL is an independent marker of poor prognosis in colorectal cancer patients. Clin Cancer Res 13(17):5070–5075PubMedCrossRef

Ulukaya E, Acilan C, Yilmaz Y (2011) Apoptosis: why and how does it occur in biology? Cell Biochem Funct 29(6):468–480PubMedCrossRef

Valnet-Rabier MB, Challier B, Thiebault S, Angonin R, Margueritte G, Mougin C, Kantelip B, Deconinck E, Cahn JY, Fest T (2005) c-FLIP protein expression in Burkitt’s lymphomas is associated with a poor clinical outcome. Br J Haematol 128(6):767–773PubMedCrossRef

Van Mau N, Kajava AV, Bonfils C, Martinou JC, Harricane MC (2005) Interactions of Bax and tBid with lipid monolayers. J Membr Biol 207(1):1–9. doi:10.1007/s00232-005-0799-7 PubMedCrossRef

Wang L, Liu Q, Zhou W, Shao H, Li F, Li X (2009) Prognostic role of myeloid cell leukemia-1 protein (Mcl-1) expression in human gastric cancer. J Surg Oncol 100(5):396–400CrossRef

Wang ZX, Yang JS, Pan X, Wang JR, Li J, Yin YM, De W (2010) Functional and biological analysis of Bcl-xL expression in human osteosarcoma. Bone 47(2):445–454PubMedCrossRef

Watanabe J, Kushihata F, Honda K, Sugita A, Tateishi N, Mominoki K, Matsuda S, Kobayashi N (2004) Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery 135(6):604–612PubMedCrossRef

Wong WWL, Puthalakath H (2008) Bcl-2 family proteins: the sentinels of the mitochondrial apoptosis pathway. IUBMB Life 60(6):390–397. doi:10.1002/iub.51 PubMedCrossRef

Woods NT, Yamaguchi H, Lee FY, Bhalla KN, Wang HG (2007) Anoikis, initiated by Mcl-1 degradation and Bim induction, is deregulated during oncogenesis. Cancer Res 67(22):10744–10752PubMedCrossRef

Yang D, Wang S, Brooks C, Dong Z, Schoenlein PV, Kumar V, Ouyang X, Xiong H, Lahat G, Hayes-Jordan A, Lazar A, Pollock R, Lev D, Liu K (2009) IFN regulatory factor 8 sensitizes soft tissue sarcoma cells to death receptor–initiated apoptosis via repression of FLICE-like protein expression. Cancer Res 69(3):1080–1088. doi:10.1158/0008-5472.can-08-2520 PubMedCrossRef

Yang X, Cao W, Zhou J, Zhang W, Zhang X, Lin W, Fei Z, Lin H, Wang B (2011) 14-3-3Zeta positive expression is associated with a poor prognosis in patients with glioblastoma. Neurosurgery 68(4):932–938PubMed

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 29(3):543–552CrossRef

Zeng Q, Chen S, You Z, Yang F, Carey TE, Saims D, Wang CY (2002) Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFκB. J Biol Chem 277(28):25203–25208. doi:10.1074/jbc.M201598200 PubMedCrossRef

Zhan M, Zhao H, Han ZC (2004) Signalling mechanisms of anoikis. Histol Histopathol 19(3):973–983PubMed

Zhang BY, Yuan F, Xiao JC, Liu BY, Jin XL (2010) Significance of expression of 14-3-3ζ protein in gastric cancer. J Shanghai Jiaotong Univ (Med Sci) 30(9):1129–1132

Zhang T, Zhao C, Luo L, Zhao H, Cheng J, Xu F (2012) The expression of Mcl-1 in human cervical cancer and its clinical significance. Med Oncol 29(3):1985–1991PubMedCrossRef

Zhu P, Tan MJ, Huang RL, Tan CK, Chong HC, Pal M, Lam CR, Boukamp P, Pan JY, Tan SH, Kersten S, Li HY, Ding JL, Tan NS (2011) Angiopoietin-like 4 protein elevates the prosurvival intracellular O₂ ⁻: H₂O₂ ratio and confers anoikis resistance to tumors. Cancer Cell 19(3):401–415PubMedCrossRef

Title: Uncovering a key to the process of metastasis in human cancers: a review of critical regulators of anoikis
Authors: Kevin Tan
David Goldstein
Philip Crowe
Jia-Lin Yang
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 11/2013
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-013-1482-5

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