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.

Hippo/YAP 通路在癌症的发展中起着重要作用。先前的研究报告称，胆汁酸可以激活 YAP（Yes Associated Protein）以促进肿瘤发生和肿瘤进展。熊去氧胆酸 (UDCA) 是一种历史悠久的老药，用于治疗胆汁淤积。到目前为止，UDCA 对结直肠癌 (CRC) 中 YAP 信号传导的影响尚未明确。本研究旨在探讨 UDCA 与 YAP 在 CRC 中的关系。UDCA 通过激活膜 G 蛋白偶联胆汁酸受体 (TGR5) 来抑制 YAP 信号。TGR5主要通过调节cAMP/PKA信号通路抑制RhoA活性，从而抑制YAP信号通路。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 CRC 模型中，UDCA 以浓度依赖性方式抑制肿瘤生长并降低 YAP 和 Ki67 的表达。UDCA 在调节 YAP 信号传导和初级胆汁酸和部分次级胆汁酸的 CRC 生长方面发挥着突出的作用，证明了维持癌症患者正常肠道胆汁酸代谢的重要性。它还为 CRC 提供了一种潜在的治疗干预措施。