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G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway
Colorectal cancer (CRC) is one of the most common cancers leading to high mortality. However, long-term administration of anti-tumor therapy for CRC is not feasible due to the side effects. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly DHA and EPA, exert protection against CRC, but t...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295433/ https://www.ncbi.nlm.nih.gov/pubmed/27506947 http://dx.doi.org/10.18632/oncotarget.11089 |
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author | Zhang, Kun Hu, Zhimei Qi, Haixia Shi, Zhemin Chang, Yanan Yao, Qingbin Cui, Hongmei Zheng, Lina Han, Yawei Han, Xiaohui Zhang, Zhen Chen, Ting Hong, Wei |
author_facet | Zhang, Kun Hu, Zhimei Qi, Haixia Shi, Zhemin Chang, Yanan Yao, Qingbin Cui, Hongmei Zheng, Lina Han, Yawei Han, Xiaohui Zhang, Zhen Chen, Ting Hong, Wei |
author_sort | Zhang, Kun |
collection | PubMed |
description | Colorectal cancer (CRC) is one of the most common cancers leading to high mortality. However, long-term administration of anti-tumor therapy for CRC is not feasible due to the side effects. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly DHA and EPA, exert protection against CRC, but the mechanisms are unclear. Here, we show that ω-3 PUFAs inhibit proliferation and induce apoptosis of CRC cells in vitro and alleviate AOM/DSS-induced mice colorectal cancer in vivo. Moreover, ω-3 PUFAs promote phosphorylation and cytoplasmic retention of YAP and this effect was mediated by MST1/2 and LATS1, suggesting that the canonical Hippo Pathway is involved in ω-3 PUFAs function. We further confirmed that increase of pYAP by ω-3 PUFAs was mediated by GPRs, including GPR40 and GPR120, which subsequently activate PKA via Gαs, thus inducing the Hippo pathway activation. These data provide a novel DHA/EPA-GPR40/120-Gαs-PKA-MST1/2-LATS1-YAP signaling pathway which is linked to ω-3 PUFAs-induced inhibition of cell proliferation and promotion of apoptosis in CRC cells, indicating a mechanism that could explain the anti-cancer action of ω-3 PUFAs. |
format | Online Article Text |
id | pubmed-5295433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-52954332017-02-08 G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway Zhang, Kun Hu, Zhimei Qi, Haixia Shi, Zhemin Chang, Yanan Yao, Qingbin Cui, Hongmei Zheng, Lina Han, Yawei Han, Xiaohui Zhang, Zhen Chen, Ting Hong, Wei Oncotarget Research Paper Colorectal cancer (CRC) is one of the most common cancers leading to high mortality. However, long-term administration of anti-tumor therapy for CRC is not feasible due to the side effects. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly DHA and EPA, exert protection against CRC, but the mechanisms are unclear. Here, we show that ω-3 PUFAs inhibit proliferation and induce apoptosis of CRC cells in vitro and alleviate AOM/DSS-induced mice colorectal cancer in vivo. Moreover, ω-3 PUFAs promote phosphorylation and cytoplasmic retention of YAP and this effect was mediated by MST1/2 and LATS1, suggesting that the canonical Hippo Pathway is involved in ω-3 PUFAs function. We further confirmed that increase of pYAP by ω-3 PUFAs was mediated by GPRs, including GPR40 and GPR120, which subsequently activate PKA via Gαs, thus inducing the Hippo pathway activation. These data provide a novel DHA/EPA-GPR40/120-Gαs-PKA-MST1/2-LATS1-YAP signaling pathway which is linked to ω-3 PUFAs-induced inhibition of cell proliferation and promotion of apoptosis in CRC cells, indicating a mechanism that could explain the anti-cancer action of ω-3 PUFAs. Impact Journals LLC 2016-08-05 /pmc/articles/PMC5295433/ /pubmed/27506947 http://dx.doi.org/10.18632/oncotarget.11089 Text en Copyright: © 2016 Zhang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhang, Kun Hu, Zhimei Qi, Haixia Shi, Zhemin Chang, Yanan Yao, Qingbin Cui, Hongmei Zheng, Lina Han, Yawei Han, Xiaohui Zhang, Zhen Chen, Ting Hong, Wei G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway |
title | G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway |
title_full | G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway |
title_fullStr | G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway |
title_full_unstemmed | G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway |
title_short | G-protein-coupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway |
title_sort | g-protein-coupled receptors mediate ω-3 pufas-inhibited colorectal cancer by activating the hippo pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295433/ https://www.ncbi.nlm.nih.gov/pubmed/27506947 http://dx.doi.org/10.18632/oncotarget.11089 |
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