TMPRSS4通过调控肝细胞癌中的CLDN1来促进癌症干细胞特性。
TMPRSS4 promotes cancer stem cell traits by regulating CLDN1 in hepatocellular carcinoma.
作者信息
Mahati Shaya, Bolati Dilinaer, Yang Ying, Mao Rui, Zhang Hua, Bao YongXing
机构信息
Department of Tumor Center, First Affiliated Hospital of Xinjiang Medical University (XJMU), Urumqi 830011, China.
Immunology Department, School of Basic Medicine, Xinjiang Medical University (XJMU), Urumqi 830011, China.
出版信息
Biochem Biophys Res Commun. 2017 Aug 26;490(3):906-912. doi: 10.1016/j.bbrc.2017.06.139. Epub 2017 Jun 23.
Encouraging advances in the treatment of hepatocellular carcinoma(HCC) have been achieved; however, a considerable part of patients still relapse or metastasize after therapy, and the underlying mechanisms have not been clarified yet. Here, we found that CLDN1 was markedly up-regulated in HCC tissues, and correlated with poor prognosis. Overexpression of CLDN1 dramatically promoted the capability of tumorsphere formation and cancer stem cell (CSC) traits. Furthermore, we found that TMPRSS4 was up-regulated in HCC tissues and there was a positive correlation between TMPRSS4 and CLDN1. In addition, the expression of CLDN1 was regulated by TMPRSS4. Moreover, TMPRSS4 mediated CSC properties and up-regulated CLDN1 by activating ERK1/2 signaling pathway. Taken together, our results revealed that CLDN1 contributed to CSC features of HCC, which was altered by TMPRSS4 expression via ERK1/2 signaling pathway, providing promising targets for novel specific therapies.
肝细胞癌（HCC）的治疗已取得令人鼓舞的进展；然而，相当一部分患者在治疗后仍会复发或转移，其潜在机制尚未阐明。在此，我们发现紧密连接蛋白1（CLDN1）在HCC组织中显著上调，并与不良预后相关。CLDN1的过表达显著促进了肿瘤球形成能力和癌症干细胞（CSC）特性。此外，我们发现跨膜丝氨酸蛋白酶4（TMPRSS4）在HCC组织中上调，且TMPRSS4与CLDN1之间存在正相关。另外，CLDN1的表达受TMPRSS4调控。而且，TMPRSS4通过激活细胞外信号调节激酶1/2（ERK1/2）信号通路介导CSC特性并上调CLDN1。综上所述，我们的结果表明CLDN1促成了HCC的CSC特征，其通过ERK1/2信号通路被TMPRSS4表达所改变，为新型特异性治疗提供了有前景的靶点。
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