Rab25 regulates integrin expression in polarized colonic epithelial cells.

ABSTRACT: Rab25 is a tumor suppressor for colon cancer in humans and mice. To identify elements of intestinal polarity regulated by Rab25, we developed Caco2-BBE cell lines stably expressing short hairpin RNA for Rab25 and lines rescuing Rab25 knockdown with reexpression of rabbit Rab25. Rab25 knockdown decreased ?2-, ?5-, and ?1-integrin expression. We observed colocalization and direct association of Rab25 with ?5?1-integrins. Rab25 knockdown also up-regulated claudin-1 expression, increased transepithelial resistance, and increased invasive behavior. Rab25-knockdown cells showed disorganized brush border microvilli with decreases in villin expression. All of these changes were reversed by reintroduction of rabbit Rab25. Rab25 knockdown altered the expression of 29 gene transcripts, including the loss of ?5-integrin transcripts. Rab25 loss decreased expression of one transcription factor, ETV4, and overexpression of ETV4 in Rab25-knockdown cells reversed losses of ?5?1-integrin. The results suggest that Rab25 controls intestinal cell polarity through the regulation of gene expression.

SUBMITTER: Krishnan M 

PROVIDER: S-EPMC3596252 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature