Rab25 regulates integrin expression in polarized colonic epithelial cells.

Krishnan M, Lapierre LA, Knowles BC, Goldenring JR
Mol Biol Cell. 2013 24 (6): 818-31

PMID: 23345591 · PMCID: PMC3596252 · DOI:10.1091/mbc.E12-10-0745

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 α2-, α5-, and β1-integrin expression. We observed colocalization and direct association of Rab25 with α5β1-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 α5-integrin transcripts. Rab25 loss decreased expression of one transcription factor, ETV4, and overexpression of ETV4 in Rab25-knockdown cells reversed losses of α5β1-integrin. The results suggest that Rab25 controls intestinal cell polarity through the regulation of gene expression.

MeSH Terms (22)

Adenovirus E1A Proteins Caco-2 Cells Cell Line, Tumor Cell Movement Cell Polarity Claudin-1 Epithelial Cells Gene Expression Regulation Gene Expression Regulation, Neoplastic HEK293 Cells Humans Integrin alpha2 Integrin alpha5 Integrin alpha5beta1 Integrin beta1 Integrins Intestinal Mucosa Microvilli Neoplasm Invasiveness Proto-Oncogene Proteins rab GTP-Binding Proteins RNA Interference

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