title: p53 regulates cytoskeleton remodeling to suppress tumor progression.
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.
authors.affiliation: Frontiers of Innovative Research in Science and Technology, Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.|Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Araki
authors.affiliation: Frontiers of Innovative Research in Science and Technology, Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ebata
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore, 169857, Singapore.
authors.forename: Alvin Kunyao
authors.initials: AK
authors.lastname: Guo
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8553, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Tobiume
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, Singapore, 117411, Singapore.
authors.forename: Steven John
authors.initials: SJ
authors.lastname: Wolf
authors.affiliation: Frontiers of Innovative Research in Science and Technology, Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. kawauchi@center.konan-u.ac.jp.|Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, Singapore, 117411, Singapore. kawauchi@center.konan-u.ac.jp.|Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan. kawauchi@center.konan-u.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawauchi
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D016023:Integrins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D020741:rho GTP-Binding Proteins
keywords: Contractile forces; ECM degradation; Focal adhesion proteins; Mechanotransduction; Metastasis; Rho GTPases; p53; p63