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Regulation and Function of Detachment-Induced Cell Death (Anoikis) in Cancer Progression and Metastasis

  • Chapter
Apoptosis, Senescence, and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Summary

Epithelial cells and possibly all normal cell types must receive adhesion-dependent signals from their microenvironments to survive. The cell death that is triggered when adherent cells detach has been termed “anoikis,” and the appreciation that tumor metastasis involves the suppression of anoikis has prompted aggressive investigation into the biochemical and molecular mechanisms that control the process. Much of this work has focused on integrins and the integrin-mediated signaling events that mediate attachment-induced normal cell survival and the molecular mechanisms that are activated in metastatic tumor cells that uncouple these responses. However, it also appears that unique cell death pathway(s) can be activated in metastatic tumor cells when conventional caspase-dependent apoptotic pathways are disrupted, some of which resemble those activated in cells undergoing autophagy (auto-digestion). Here, we will review what is known about the signaling pathways that control attachment-mediated survival in normal cells and the molecular alterations that appear to disrupt these pathways in metastatic cells. We will also review the evidence that alternative cell death mechanism(s) can be activated in metastatic tumors when apoptosis is disrupted.

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Authors
  1. David J. McConkey PhD
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  2. Victor Bondar MD
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA

    David A. Gewirtz

  2. Departments of Medicine, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Shawn E. Holt

  3. Departments of Pathology, Human Genetics, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Steven Grant

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McConkey, D.J., Bondar, V. (2007). Regulation and Function of Detachment-Induced Cell Death (Anoikis) in Cancer Progression and Metastasis. In: Gewirtz, D.A., Holt, S.E., Grant, S. (eds) Apoptosis, Senescence, and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-221-2_6

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  • DOI: https://doi.org/10.1007/978-1-59745-221-2_6

  • Publisher Name: Humana Press

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  • Online ISBN: 978-1-59745-221-2

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