E6/E7-P53-POU2F1-CTHRC1 轴促进宫颈癌转移并激活 Wnt/PCP 通路。
E6/E7-P53-POU2F1-CTHRC1 axis promotes cervical cancer metastasis and activates Wnt/PCP pathway.
机构信息
Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China.
Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
出版信息
Sci Rep. 2017 Mar 17;7:44744. doi: 10.1038/srep44744.
Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis.
宫颈癌是一种传染性癌症，也是全球最常见的妇科癌症。高危黏膜型人乳头瘤病毒的早期基因 E6/E7 在宫颈癌的致癌过程中发挥着关键作用。然而，其在调节肿瘤微环境，特别是细胞外基质（ECM）方面的作用却知之甚少。在这项研究中，我们发现 E6/E7 可以调节多种 ECM 蛋白，特别是富含三螺旋结构域的胶原蛋白 1（CTHRC1）。CTHRC1 在宫颈癌组织和血清中高表达，并与临床病理参数密切相关。CTHRC1 促进宫颈癌细胞在体外的迁移和侵袭，以及体内的转移。E6/E7 通过 E6/E7-p53-POU2F1（POU 类 2 同源框 1）轴调节宫颈癌中 CTHRC1 的表达。此外，CTHRC1 激活了 Wnt/PCP 信号通路。综上所述，E6/E7-p53-POU2F1-CTHRC1 轴促进了宫颈癌细胞的侵袭和转移，可能成为干预宫颈癌侵袭和转移的潜在治疗靶点。
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