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p53 regulates cytoskeleton remodeling to suppress tumor progression

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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.

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Acknowledgments

We thank Dr. Shota Yamauchi and Mr. Toshiya Kotari for discussion. This work was supported by JSPS KAKENHI Grant Number 26890024.

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Authors and Affiliations

  1. Frontiers of Innovative Research in Science and Technology, Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan

    Keigo Araki, Takahiro Ebata & Keiko Kawauchi

  2. Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan

    Keigo Araki

  3. Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore, 169857, Singapore

    Alvin Kunyao Guo

  4. Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8553, Japan

    Kei Tobiume

  5. Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, Singapore, 117411, Singapore

    Steven John Wolf & Keiko Kawauchi

  6. Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan

    Keiko Kawauchi

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  1. Keigo Araki
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Araki, K., Ebata, T., Guo, A.K. et al. p53 regulates cytoskeleton remodeling to suppress tumor progression. Cell. Mol. Life Sci. 72, 4077–4094 (2015). https://doi.org/10.1007/s00018-015-1989-9

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