Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis.
Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis.
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熊去氧胆酸通过TGR5-YAP轴抑制结直肠癌恶性进展
DOI：
10.1038/s41420-021-00589-8
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发表时间：
2021-08-07
影响因子：
7
通讯作者：
Bi F
中科院分区：
文献类型：
--
作者：
Zhang H;Xu H;Zhang C;Tang Q;Bi F
河马/YAP通路在肿瘤的发生发展中起着重要作用。先前的研究报告胆汁酸可以激活YAP(是相关蛋白)来促进肿瘤的发生和肿瘤的进展。熊去氧胆酸(UDCA)是一种历史悠久的治疗胆汁淤积症的药物。到目前为止，UDCA对YAP信号转导通路在结直肠癌中的作用还不是很清楚。本研究旨在探讨结直肠癌中UDCA与YAP的关系。UDCA通过激活细胞膜G蛋白偶联胆汁酸受体(TGR5)抑制YAP信号。TGR5主要调控cAMP/PKA信号通路，抑制RhoA活性，从而抑制YAP信号转导。此外，YAP表达的恢复减轻了UDCA对CRC细胞增殖的抑制作用。在AOM/DSS诱导的结直肠癌模型中，UDCA以浓度依赖的方式抑制肿瘤生长，并降低YAP和Ki67的表达。UDCA从初级胆汁酸和部分次级胆汁酸出发，在调节YAP信号和结直肠癌生长方面发挥了显著作用，表明了癌症患者维持正常的肠道胆汁酸代谢的重要性。这也为结直肠癌提供了一种潜在的治疗干预方法。
The Hippo/YAP pathway plays an important role in the development of cancers. Previous studies have reported that bile acids can activate YAP (Yes Associated Protein) to promote tumorigenesis and tumor progression. Ursodeoxycholic acid (UDCA) is a long-established old drug used for cholestasis treatment. So far, the effect of UDCA on YAP signaling in colorectal cancer (CRC) is not well defined. This study means to explore relationship of UDCA and YAP in CRC. UDCA suppressed YAP signaling by activating the membrane G-protein-coupled bile acid receptor (TGR5). TGR5 mainly regulated cAMP/PKA signaling pathway to inhibit RhoA activity, thereby suppressing YAP signaling. Moreover, the restoration of YAP expression alleviated the inhibitory effect of UDCA on CRC cell proliferation. In AOM/DSS-induced CRC model, UDCA inhibited tumor growth in a concentration-dependent manner and decreased expression of YAP and Ki67. UDCA plays a distinguished role in regulating YAP signaling and CRC growth from the primary bile acids and partial secondary bile acids, demonstrating the importance of maintaining normal intestinal bile acid metabolism in cancer patients. It also presents a potential therapeutic intervention for CRC.
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影响因子：
9.7
作者：
Im, E;Choi, SH;Kim, ND
通讯作者：
Kim, ND
影响因子：
9.7
作者：
Im, EO;Choi, YH;Kim, ND
通讯作者：
Kim, ND
影响因子：
4.7
作者：
Oyama, K;Shiota, G;Kawasaki, H
通讯作者：
Kawasaki, H
影响因子：
16.6
作者：
Oakes PW;Wagner E;Brand CA;Probst D;Linke M;Schwarz US;Glotzer M;Gardel ML
通讯作者：
Gardel ML
DOI：
10.1016/bs.pmbts.2015.02.005
发表时间：
2015
影响因子：
--
作者：
Kennedy JE;Marchese A
通讯作者：
Marchese A