AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin.

ABSTRACT: Loss of epithelial polarity impacts organ development and function; it is also oncogenic. AMPK, a key sensor of metabolic stress stabilizes cell-cell junctions and maintains epithelial polarity; its activation by Metformin protects the epithelial barrier against stress and suppresses tumorigenesis. How AMPK protects the epithelium remains unknown. Here, we identify GIV/Girdin as a novel effector of AMPK, whose phosphorylation at a single site is both necessary and sufficient for strengthening mammalian epithelial tight junctions and preserving cell polarity and barrier function in the face of energetic stress. Expression of an oncogenic mutant of GIV (cataloged in TCGA) that cannot be phosphorylated by AMPK increased anchorage-independent growth of tumor cells and helped these cells to eva

SUBMITTER: Aznar N 

PROVIDER: S-EPMC5119889 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature