OS 15-07 ROLE OF (PRO) RENIN RECEPTOR IN THE ACTIVATION OF WNT/ β-CATENIN PATHWAY IN COLON CANCER.

OBJECTIVE: Constitutive activation of Wnt/β-catenin pathway plays an important role in the pathogenesis of colon cancer; however, recent studies have also indicated that elevated Wnt levels are essential. In the present study, we investigated the potential role of (pro) renin receptor in the pathophysiology of colon cancer.

DESIGN AND METHOD: (P) RR expression in human colon tissues was measured by immunohistochemistry and Western blot analysis. Human colon cancer cell lines DLD-1 with adenomatous polyposis coli (APC) truncated mutation, and HCT116 withβ-catenin activating mutation, were transfected with scramble siRNA and siRNA against (pro) renin receptor.

RESULTS: (Pro) renin receptor expression was significantly increased in colon cancer tissue. (Pro) renin receptor knockdown significantly decreased protein levels of the main components of Wnt/β-catenin pathway (Wnt, phosphorylated-LRP6, active β-catenin and cyclin D1) in both DLD-1 and HCT116 cells. Wnt signaling activity, measured by Tcf/Wnt signaling reporter assay, was also significantly decreased by (pro) renin receptor knockdown. WST-1 assay showed that (pro) renin receptor knockdown markedly reduced cell proliferation activity.

CONCLUSIONS: These data suggest that (pro) renin receptor promotes colon cancer through Wnt/β-catenin pathway despite of intrinsic its constitutive activation.