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(Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations

BACKGROUND: Although constitutive activating mutations in the Wnt/β-catenin signalling pathway are important for colorectal cancer development, canonical signalling through Wnt ligands is essential for β-catenin activation. Here, we investigated the role of (pro)renin receptor ((P)RR), a component o...

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Autores principales: Wang, Juan, Shibayama, Yuki, Zhang, Anqi, Ohsaki, Hiroyuki, Asano, Eisuke, Suzuki, Yasuyuki, Kushida, Yoshio, Kobara, Hideki, Masaki, Tsutomu, Wang, Zhiyu, Nishiyama, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342928/
https://www.ncbi.nlm.nih.gov/pubmed/30555158
http://dx.doi.org/10.1038/s41416-018-0350-0
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author Wang, Juan
Shibayama, Yuki
Zhang, Anqi
Ohsaki, Hiroyuki
Asano, Eisuke
Suzuki, Yasuyuki
Kushida, Yoshio
Kobara, Hideki
Masaki, Tsutomu
Wang, Zhiyu
Nishiyama, Akira
author_facet Wang, Juan
Shibayama, Yuki
Zhang, Anqi
Ohsaki, Hiroyuki
Asano, Eisuke
Suzuki, Yasuyuki
Kushida, Yoshio
Kobara, Hideki
Masaki, Tsutomu
Wang, Zhiyu
Nishiyama, Akira
author_sort Wang, Juan
collection PubMed
description BACKGROUND: Although constitutive activating mutations in the Wnt/β-catenin signalling pathway are important for colorectal cancer development, canonical signalling through Wnt ligands is essential for β-catenin activation. Here, we investigated the role of (pro)renin receptor ((P)RR), a component of the Wnt receptor complex, in the pathogenesis of colorectal cancer. METHODS: (P)RR silencing was performed in human colorectal cancer cells containing constitutive activating mutations in the Wnt/β-catenin pathway. (P)RR overexpression was induced in normal colon epithelial cells. Protein and mRNA levels of pathway components were detected, and Wnt signalling activity was measured using a β-catenin reporter. Cell proliferative activity and apoptosis were evaluated using WST-1 assay and flow cytometry. Xenografts were induced in nude mice. RESULTS: (P)RR expression was greater in colorectal cancer tissues and cells than in normal colorectal samples. Patients with strong (P)RR expression took more proportion in groups with poorly-differentiated, advanced and rapidly-progressing cancers. (P)RR silencing attenuated the pathway in colorectal cancer cells, impaired their proliferation in vitro and vivo. (P)RR overexpression enhanced the pathway and proliferation of normal colon epithelial cells. CONCLUSIONS: Aberrant (P)RR expression promotes colorectal cancer through the Wnt/β-catenin signalling pathway despite constitutive pathway-activating mutations. (P)RR is a potential diagnostic and therapeutic target for colorectal cancer.
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spelling pubmed-63429282019-12-17 (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations Wang, Juan Shibayama, Yuki Zhang, Anqi Ohsaki, Hiroyuki Asano, Eisuke Suzuki, Yasuyuki Kushida, Yoshio Kobara, Hideki Masaki, Tsutomu Wang, Zhiyu Nishiyama, Akira Br J Cancer Article BACKGROUND: Although constitutive activating mutations in the Wnt/β-catenin signalling pathway are important for colorectal cancer development, canonical signalling through Wnt ligands is essential for β-catenin activation. Here, we investigated the role of (pro)renin receptor ((P)RR), a component of the Wnt receptor complex, in the pathogenesis of colorectal cancer. METHODS: (P)RR silencing was performed in human colorectal cancer cells containing constitutive activating mutations in the Wnt/β-catenin pathway. (P)RR overexpression was induced in normal colon epithelial cells. Protein and mRNA levels of pathway components were detected, and Wnt signalling activity was measured using a β-catenin reporter. Cell proliferative activity and apoptosis were evaluated using WST-1 assay and flow cytometry. Xenografts were induced in nude mice. RESULTS: (P)RR expression was greater in colorectal cancer tissues and cells than in normal colorectal samples. Patients with strong (P)RR expression took more proportion in groups with poorly-differentiated, advanced and rapidly-progressing cancers. (P)RR silencing attenuated the pathway in colorectal cancer cells, impaired their proliferation in vitro and vivo. (P)RR overexpression enhanced the pathway and proliferation of normal colon epithelial cells. CONCLUSIONS: Aberrant (P)RR expression promotes colorectal cancer through the Wnt/β-catenin signalling pathway despite constitutive pathway-activating mutations. (P)RR is a potential diagnostic and therapeutic target for colorectal cancer. Nature Publishing Group UK 2018-12-17 2019-01-22 /pmc/articles/PMC6342928/ /pubmed/30555158 http://dx.doi.org/10.1038/s41416-018-0350-0 Text en © Cancer Research UK 2018 https://creativecommons.org/licenses/by/4.0/This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Wang, Juan
Shibayama, Yuki
Zhang, Anqi
Ohsaki, Hiroyuki
Asano, Eisuke
Suzuki, Yasuyuki
Kushida, Yoshio
Kobara, Hideki
Masaki, Tsutomu
Wang, Zhiyu
Nishiyama, Akira
(Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations
title (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations
title_full (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations
title_fullStr (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations
title_full_unstemmed (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations
title_short (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations
title_sort (pro)renin receptor promotes colorectal cancer through the wnt/beta-catenin signalling pathway despite constitutive pathway component mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342928/
https://www.ncbi.nlm.nih.gov/pubmed/30555158
http://dx.doi.org/10.1038/s41416-018-0350-0
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