Rab25 regulates integrin expression in polarized colonic epithelial cells

Autor: Moorthy Krishnan, Byron C. Knowles, Lynne A. Lapierre, James R. Goldenring
Rok vydání: 2013
Předmět:
Integrins
Integrin alpha2
Integrin alpha5
digestive system
Small hairpin RNA
03 medical and health sciences
0302 clinical medicine
Intestinal mucosa
Cell Movement
RNA interference
Cell Line
Tumor
Proto-Oncogene Proteins
Claudin-1
Cell polarity
Humans
Neoplasm Invasiveness
Intestinal Mucosa
Molecular Biology
030304 developmental biology
Regulation of gene expression
0303 health sciences
Gene knockdown
Microvilli
Proto-Oncogene Proteins c-ets
biology
Integrin beta1
HEK 293 cells
Cell Polarity
Epithelial Cells
Articles
Cell Biology
Molecular biology
Cell biology
Gene Expression Regulation
Neoplastic
HEK293 Cells
Gene Expression Regulation
rab GTP-Binding Proteins
Membrane Trafficking
030220 oncology & carcinogenesis
biology.protein
RNA Interference
Adenovirus E1A Proteins
Caco-2 Cells
Villin
Integrin alpha5beta1
Zdroj: Molecular Biology of the Cell
ISSN: 1939-4586
1059-1524
Popis: Rab25 is a tumor suppressor in the colon, but the mechanisms underlying the influence of Rab25 on polarity are unknown. Findings on changes in polarity in Caco2-BBE cells with knockdown and rescue of Rab25 expression indicate that Rab25 regulates integrin gene expression mediated by ETV4.
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.
Databáze: OpenAIRE
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