Opposing Roles of Wild-type and Mutant p53 in the Process of Epithelial to Mesenchymal Transition

Oleg Semenov; Alexandra Daks; Olga Fedorova; Oleg Shuvalov; Nickolai A Barlev

doi:10.3389/fmolb.2022.928399

Opposing Roles of Wild-type and Mutant p53 in the Process of Epithelial to Mesenchymal Transition

Front Mol Biosci. 2022 Jun 23:9:928399. doi: 10.3389/fmolb.2022.928399. eCollection 2022.

Authors

Oleg Semenov¹, Alexandra Daks¹, Olga Fedorova¹, Oleg Shuvalov¹, Nickolai A Barlev^{1

2

3}

Affiliations

¹ Regulation of Gene Expression Laboratory, Institute of Cytology RAS, Saint-Petersburg, Russia.
² Laboratory of Intracellular Signalling, Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
³ The Group of Targeted Delivery Mechanisms of Nanosystems, Institute of Biomedical Chemistry, Moscow, Russia.

Abstract

The central role of an aberrantly activated EMT program in defining the critical features of aggressive carcinomas is well documented and includes cell plasticity, metastatic dissemination, drug resistance, and cancer stem cell-like phenotypes. The p53 tumor suppressor is critical for leashing off all the features mentioned above. On the molecular level, the suppression of these effects is exerted by p53 via regulation of its target genes, whose products are involved in cell cycle, apoptosis, autophagy, DNA repair, and interactions with immune cells. Importantly, a set of specific mutations in the TP53 gene (named Gain-of-Function mutations) converts this tumor suppressor into an oncogene. In this review, we attempted to contrast different regulatory roles of wild-type and mutant p53 in the multi-faceted process of EMT.

Keywords: EMT; epigenetic regulation; epithelial to mesenchymal transition; microRNA; mutant p53; p53; wild-type p53.

Publication types

Review