(Pro)renin receptor is crucial for Wnt/β-catenin-dependent genesis of pancreatic ductal adenocarcinoma

Yuki Shibayama, Takayuki Fujimori, Genevieve Nguyen, Takuo Hirose, Kazuhito Totsune, Atsuhiro Ichihara, Kento Kitada, Daisuke Nakano, Hiroyuki Kobori, Masakazu Kohno, Tsutomu Masaki, Yasuyuki Suzuki, Shinichi Yachida, Akira Nishiyama

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22 Citations (Scopus)

Abstract

Although Wnt/β-catenin signaling is known to be aberrantly activated in PDAC, mutations of CTNNB1, APC or other pathway components are rare in this tumor type, suggesting alternative mechanisms for Wnt/β-catenin activation. Recent studies have implicated the (pro)renin receptor ((P)RR) is related to the Wnt/β-catenin signaling pathway. We therefore investigated the possible role of (P)RR in pancreatic carcinogenesis. Plasma s(P)RR levels were significantly (P < 0.0001) higher in patients with PDAC than in healthy matched controls. We also identified aberrant expression of (P)RR in premalignant PanIN and PDAC lesions and all the PDAC cell lines examined. Inhibiting (P)RR with an siRNA attenuated activation of Wnt/β-catenin signaling pathway and reduced the proliferative ability of PDAC cells in vitro and the growth of engrafted tumors in vivo. Loss of (P)RR induced apoptosis of human PDAC cells. This is the first demonstration that (P)RR may be profoundly involved in ductal tumorigenesis in the pancreas.

Original languageEnglish
Article number8854
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Mar 9

ASJC Scopus subject areas

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    Shibayama, Y., Fujimori, T., Nguyen, G., Hirose, T., Totsune, K., Ichihara, A., Kitada, K., Nakano, D., Kobori, H., Kohno, M., Masaki, T., Suzuki, Y., Yachida, S., & Nishiyama, A. (2015). (Pro)renin receptor is crucial for Wnt/β-catenin-dependent genesis of pancreatic ductal adenocarcinoma. Scientific reports, 5, [8854]. https://doi.org/10.1038/srep08854