Obstetrics and Gynecology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Obstetrics and Gynecology Department, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, 710038, China.
Obstetrics and Gynecology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Exp Cell Res. 2020 Nov 1;396(1):112248. doi: 10.1016/j.yexcr.2020.112248. Epub 2020 Aug 24.
Accumulating evidence has suggested that thyroid hormone receptor interacting protein 6 (TRIP6) is a novel tumor-related regulator that is aberrantly expressed in multiple tumors and contributes to tumor progression and metastasis. Yet, little is known about the role of TRIP6 in cervical cancer. In the current study, we aimed to explore the expression, biological function, and regulatory mechanism of TRIP6 in cervical cancer. Here we showed that TRIP6 expression was markedly upregulated in cervical cancer tissues and cell lines. The knockdown of TRIP6 suppressed the proliferation, colony formation, and invasive potential of cervical cancer cells, whereas TRIP6 overexpression exhibited the opposite effect. Moreover, TRIP6 contributes to the activation of Yes-associated protein (YAP) by downregulating the level of YAP phosphorylation. Notably, TRIP6-mediated tumor promotion effect was partially reversed by YAP inhibition. In addition, TRIP6 knockdown retarded the in vivo tumor growth of cervical cancer of mouse xenograft models associated with downregulation of YAP activation in tumor tissues. Taken together, these results reveal a potential tumor promotion role of TRIP6 that facilitates the proliferation and invasion of cervical cancer through activation of YAP. Our study underlines the importance of the TRIP6/YAP axis in cervical cancer and suggests TRIP6 as a potential anticancer candidate for cervical cancer.
越来越多的证据表明，甲状腺激素受体相互作用蛋白 6（TRIP6）是一种新型的肿瘤相关调节因子，在多种肿瘤中异常表达，并促进肿瘤的进展和转移。然而，关于 TRIP6 在宫颈癌中的作用知之甚少。在本研究中，我们旨在探讨 TRIP6 在宫颈癌中的表达、生物学功能和调控机制。研究结果显示，TRIP6 在宫颈癌组织和细胞系中表达明显上调。TRIP6 敲低抑制了宫颈癌细胞的增殖、集落形成和侵袭能力，而 TRIP6 过表达则表现出相反的效果。此外，TRIP6 通过下调 YAP 磷酸化水平来促进 YAP 的激活。值得注意的是，YAP 抑制部分逆转了 TRIP6 介导的肿瘤促进作用。此外，TRIP6 敲低与肿瘤组织中 YAP 激活的下调相关，可减缓宫颈癌小鼠异种移植模型的体内肿瘤生长。综上所述，这些结果揭示了 TRIP6 通过激活 YAP 促进宫颈癌增殖和侵袭的潜在肿瘤促进作用。我们的研究强调了 TRIP6/YAP 轴在宫颈癌中的重要性，并表明 TRIP6 可能成为宫颈癌的潜在抗癌候选物。
