p53 regulates cytoskeleton remodeling to suppress tumor progression

Cell Mol Life Sci. 2015 Nov;72(21):4077-94. doi: 10.1007/s00018-015-1989-9. Epub 2015 Jul 24.

Abstract

Cancer cells possess unique characteristics such as invasiveness, the ability to undergo epithelial-mesenchymal transition, and an inherent stemness. Cell morphology is altered during these processes and this is highly dependent on actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is, therefore, important for determination of cell fate. Mutations within the TP53 (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the protein are often observed in aggressive cancer cells. Here, we highlight the roles of p53 and its GOF mutants in cancer cell invasion from the perspective of the actin cytoskeleton; in particular its reorganization and regulation by cell adhesion molecules such as integrins and cadherins. We emphasize the multiple functions of p53 in the regulation of actin cytoskeleton remodeling in response to the extracellular microenvironment, and oncogene activation. Such an approach provides a new perspective in the consideration of novel targets for anti-cancer therapy.

Keywords: Contractile forces; ECM degradation; Focal adhesion proteins; Mechanotransduction; Metastasis; Rho GTPases; p53; p63.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / pathology
  • Animals
  • Cadherins / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Movement
  • Cytoskeleton / metabolism*
  • Humans
  • Integrins / metabolism
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Cadherins
  • Cell Adhesion Molecules
  • Integrins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • rho GTP-Binding Proteins