Mutant p53 and NOX4 are modulators of a CCL5-driven pro-migratory secretome.

ABSTRACT: Previously, we showed wild-type (WT) and mutant (mt) forms of p53 differentially regulate ROS generation by NADPH oxidase-4 (NOX4). We found that WT-p53 suppresses TGF-β-induced NOX4, ROS production, and cell migration, whereas tumor-associated mt-p53 proteins enhance NOX4 expression and cell migration by TGF-β/SMAD3-dependent mechanisms. In this study, we investigated the role of mutant p53-induced NOX4 on the cancer cell secretome and the effects NOX4 signaling have on the tumor microenvironment (TME). We found conditioned media collected from H1299 lung epithelial cells stably expressing either mutant p53-R248Q or R273H promotes the migration and invasion of naïve H1299 cells and chemotactic recruitment of THP-1 monocytes. These effects were diminished with conditioned media from cells

SUBMITTER: Boudreau HE 

PROVIDER: S-EPMC10081791 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature