Kevin Tan1, David Goldstein, Philip Crowe, Jia-Lin Yang. 1. 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.
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-(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. 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.
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 humancancer 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 humancancer 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 humancancer 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. 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 humancancer. These regulators of anoikis might therefore be the targets for developing therapies to overcome anoikis resistance in metastatic cancer.
Authors: Imtiaz A Mawji; Craig D Simpson; Rose Hurren; Marcela Gronda; Moyo A Williams; Jorge Filmus; James Jonkman; Ralph S Da Costa; Brian C Wilson; Michael P Thomas; John C Reed; Gennadi V Glinsky; Aaron D Schimmer Journal: J Natl Cancer Inst Date: 2007-05-16 Impact factor: 13.506
Authors: James L Chen; Jason David; Douglas Cook-Spaeth; Sydney Casey; David Cohen; Karuppaiyah Selvendiran; Tanios Bekaii-Saab; John L Hays Journal: Mol Cancer Res Date: 2016-11-02 Impact factor: 5.852
Authors: Victoria L Herrera; Julius L Decano; Glaiza A Tan; Ann M Moran; Khristine A Pasion; Yuichi Matsubara; Nelson Ruiz-Opazo Journal: PLoS One Date: 2014-01-21 Impact factor: 3.240