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

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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.

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  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

    Kevin Tan & Jia-Lin Yang

  2. Department of Medical Oncology, Faculty of Medicine, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia

    David Goldstein

  3. Department of Surgery, Faculty of Medicine, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia

    Philip Crowe & Jia-Lin Yang

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Correspondence to Jia-Lin Yang.

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Tan, K., Goldstein, D., Crowe, P. et al. Uncovering a key to the process of metastasis in human cancers: a review of critical regulators of anoikis. J Cancer Res Clin Oncol 139, 1795–1805 (2013). https://doi.org/10.1007/s00432-013-1482-5

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  • DOI: https://doi.org/10.1007/s00432-013-1482-5

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