title: Uncovering a key to the process of metastasis in human cancers: a review of critical regulators of anoikis.
abstract: OBJECTIVE
  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-(xL), 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-(xL), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Adult Cancer Program, Sarcoma and Nano-Oncology Research Group, Faculty of Medicine, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Room 209, Sydney, NSW, 2052, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tan
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Philip
authors.initials: P
authors.lastname: Crowe
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Yang
mesh_terms: D000818:Animals; D023102:Anoikis / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*
references.citation: Semin Cancer Biol. 2006 Jun;16(3):183-92
references.pmid: 16697662
references.citation: Clin Cancer Res. 2007 Sep 1;13(17):5070-5
references.pmid: 17785559
references.citation: Sci STKE. 2005 Aug 09;2005(296):re10
references.pmid: 16091624
references.citation: Med Oncol. 2012 Sep;29(3):1985-91
references.pmid: 21674276
references.citation: Cancer Res. 2009 Feb 1;69(3):1080-8
references.pmid: 19155307
references.citation: Cancer Biol Ther. 2005 Feb;4(2):139-63
references.pmid: 15725726
references.citation: Int J Cell Biol. 2012;2012:306879
references.pmid: 22505926
references.citation: Br J Haematol. 2005 Mar;128(6):767-73
references.pmid: 15755279
references.citation: Biochim Biophys Acta. 2009 Dec;1796(2):293-308
references.pmid: 19683560
references.citation: Expert Opin Ther Targets. 2010 Dec;14(12):1343-54
references.pmid: 21058923
references.citation: J Biol Chem. 2008 Oct 17;283(42):28029-37
references.pmid: 18703509
references.citation: Oncol Rep. 2008 Jan;19(1):117-22
references.pmid: 18097584
references.citation: Cancers (Basel). 2011 Jun;3(2):1639-71
references.pmid: 22348197
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Int J Mol Sci. 2012;13(5):5818-5831
references.pmid: 22754333
references.citation: Cell. 2008 Dec 12;135(6):1074-84
references.pmid: 19062087
references.citation: Int J Biochem Cell Biol. 2005 Feb;37(2):267-71
references.pmid: 15474972
references.citation: Cancer Res. 2013 Feb 15;73(4):1352-61
references.pmid: 23248118
references.citation: Annu Rev Pharmacol Toxicol. 2000;40:617-47
references.pmid: 10836149
references.citation: Am J Physiol Cell Physiol. 2012 May 1;302(9):C1284-92
references.pmid: 22277751
references.citation: Histol Histopathol. 2004 Jul;19(3):973-83
references.pmid: 15168359
references.citation: Mol Cancer Res. 2012 Nov;10(11):1482-95
references.pmid: 22952044
references.citation: J Invest Dermatol. 2009 Jul;129(7):1703-9
references.pmid: 19242522
references.citation: Blood. 2008 Nov 1;112(9):3807-17
references.pmid: 18599795
references.citation: Mol Aspects Med. 2010 Apr;31(2):205-14
references.pmid: 20153362
references.citation: Oncol Rep. 2011 Mar;25(3):661-7
references.pmid: 21206976
references.citation: J Biol Chem. 2002 Jul 12;277(28):25203-8
references.pmid: 11994287
references.citation: Cancer Res. 2001 Jun 15;61(12):4837-41
references.pmid: 11406560
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):162-7
references.pmid: 18162532
references.citation: J Biol Chem. 2006 Jun 30;281(26):17758-67
references.pmid: 16632475
references.citation: J Orthop Res. 2011 Jan;29(1):143-51
references.pmid: 20661931
references.citation: Oncogene. 2007 Feb 26;26(9):1324-37
references.pmid: 17322918
references.citation: Cancer Lett. 2013 Jun 10;333(2):147-51
references.pmid: 23376255
references.citation: Oncotarget. 2011 Apr;2(4):305-12
references.pmid: 21471610
references.citation: Cancer Res. 2007 Aug 15;67(16):7901-6
references.pmid: 17699796
references.citation: World J Gastroenterol. 2008 Jan 21;14(3):428-34
references.pmid: 18200666
references.citation: Semin Cell Dev Biol. 2011 Sep;22(7):663-72
references.pmid: 21920446
references.citation: J Cell Biochem. 2005 Jul 1;95(4):670-87
references.pmid: 15861397
references.citation: Arch Immunol Ther Exp (Warsz). 2013 Feb;61(1):43-58
references.pmid: 23229678
references.citation: IUBMB Life. 2008 Jun;60(6):390-7
references.pmid: 18425793
references.citation: Cell Death Differ. 2010 Sep;17(9):1463-73
references.pmid: 20224598
references.citation: Annu Rev Cell Dev Biol. 2006;22:287-309
references.pmid: 16824016
references.citation: Cancer Immunol Immunother. 2011 Aug;60(8):1173-80
references.pmid: 21626033
references.citation: Mol Cancer Res. 2012 Jun;10(6):677-88
references.pmid: 22661548
references.citation: PLoS One. 2011;6(8):e23840
references.pmid: 21886829
references.citation: Int J Biochem Cell Biol. 2010 Feb;42(2):210-3
references.pmid: 19932761
references.citation: Chin J Cancer. 2013 Mar;32(3):121-9
references.pmid: 23114086
references.citation: Mol Cancer Res. 2009 Apr;7(4):549-56
references.pmid: 19372583
references.citation: Pediatr Blood Cancer. 2013 Apr;60(4):575-9
references.pmid: 23255321
references.citation: Cell Death Differ. 2009 Aug;16(8):1075-82
references.pmid: 19521421
references.citation: Cell Biochem Funct. 2011 Aug;29(6):468-80
references.pmid: 21773978
references.citation: Oncogene. 2003 Dec 8;22(56):9030-40
references.pmid: 14663481
references.citation: Bone. 2010 Aug;47(2):445-54
references.pmid: 20580954
references.citation: Neoplasia. 2010 Feb;12(2):128-38
references.pmid: 20126471
references.citation: J Natl Cancer Inst. 2007 May 16;99(10):811-22
references.pmid: 17505076
references.citation: Nat Cell Biol. 2003 Jan;5(1):28-37
references.pmid: 12510191
references.citation: Expert Opin Ther Targets. 2012 May;16(5):515-23
references.pmid: 22512284
references.citation: Biochem J. 2002 Dec 15;368(Pt 3):915-21
references.pmid: 12193163
references.citation: Acta Histochem. 2011 Dec;113(8):810-4
references.pmid: 21277008
references.citation: Nat Cell Biol. 2004 May;6(5):388-9
references.pmid: 15122265
references.citation: Cancer Lett. 2008 Dec 18;272(2):177-85
references.pmid: 18579285
references.citation: Curr Opin Cell Biol. 2005 Dec;17(6):626-30
references.pmid: 16219456
references.citation: Clin Cancer Res. 2007 Dec 15;13(24):7254-63
references.pmid: 18094405
references.citation: Cancer Res. 2008 Mar 15;68(6):1760-7
references.pmid: 18339856
references.citation: Cancer Sci. 2008 Mar;99(3):543-52
references.pmid: 18201274
references.citation: Biochem Pharmacol. 2008 Dec 1;76(11):1352-64
references.pmid: 18708031
references.citation: J Surg Oncol. 2009 Oct 1;100(5):396-400
references.pmid: 19582795
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1528-32
references.pmid: 18218778
references.citation: Jpn J Cancer Res. 2002 May;93(5):542-50
references.pmid: 12036450
references.citation: Cancer Res. 2007 Nov 15;67(22):10744-52
references.pmid: 18006817
references.citation: Endocr Relat Cancer. 2011 Sep 20;18(5):613-26
references.pmid: 21813730
references.citation: Cancer Res. 2009 Apr 15;69(8):3425-32
references.pmid: 19318578
references.citation: Invest New Drugs. 2012 Feb;30(1):48-58
references.pmid: 20694504
references.citation: Oncogene. 2002 Apr 25;21(18):2908-13
references.pmid: 11973652
references.citation: J Pathol. 2012 Jan;226(2):380-93
references.pmid: 21953325
references.citation: Cancer Cell. 2011 Mar 8;19(3):401-15
references.pmid: 21397862
references.citation: Int J Oncol. 2006 Jan;28(1):25-32
references.pmid: 16327976
references.citation: Dev Dyn. 2010 Nov;239(11):2795-805
references.pmid: 20925119
references.citation: J Membr Biol. 2005 Sep;207(1):1-9
references.pmid: 16463138
references.citation: Science. 1998 Aug 28;281(5381):1309-12
references.pmid: 9721092
references.citation: Clin Cancer Res. 2011 Sep 15;17(18):5973-81
references.pmid: 21821698
references.citation: J Orthop Res. 2011 Jul;29(7):1131-6
references.pmid: 21319215
references.citation: J Surg Res. 2010 Dec;164(2):301-8
references.pmid: 20031162
references.citation: Neurosurgery. 2011 Apr;68(4):932-8; discussion 938
references.pmid: 21242845
references.citation: Cell. 2004 Mar 5;116(5):751-62
references.pmid: 15006356
references.citation: Curr Opin Cell Biol. 2001 Oct;13(5):555-62
references.pmid: 11544023
references.citation: Cancer Sci. 2011 Nov;102(11):1943-8
references.pmid: 21812858
references.citation: Mol Cell Biol. 2007 Nov;27(21):7649-60
references.pmid: 17785447
references.citation: Int J Gynecol Cancer. 2005 Jul-Aug;15(4):663-70
references.pmid: 16014121
references.citation: Adv Enzyme Regul. 2006;46:163-75
references.pmid: 16857240
references.citation: Mol Cancer Ther. 2009 Dec;8(12):3173-80
references.pmid: 19934277
references.citation: Surgery. 2004 Jun;135(6):604-12
references.pmid: 15179366