CMTM6 通过稳定 β-连环蛋白促进肝细胞癌进展。

CMTM6 promotes hepatocellular carcinoma progression through stabilizing β-catenin.

机构信息

Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China; Peking University Center for Human Disease Genomics, Beijing, China, Beijing, China.

Central Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Shandong, China.

出版信息

Cancer Lett. 2024 Feb 28;583:216585. doi: 10.1016/j.canlet.2023.216585. Epub 2023 Dec 13.

DOI:10.1016/j.canlet.2023.216585

PMID:38101607

Abstract

CMTM6, a regulator of PD-L1 stability, has been implicated in the development of various cancers. However, the expression and role of CMTM6 in hepatocellular carcinoma (HCC) remains controversial. Our study revealed a negative correlation between CMTM6 expression and HCC prognosis through bioinformatics analysis and immunofluorescence staining. CMTM6 expression was also positively associated with alpha-fetoprotein (AFP) levels, supporting its potential as a prognostic marker for HCC. Using Cmtm6 knockout mice, we found that Cmtm6 deficiency inhibited HCC formation and cell proliferation in primary liver cancer models induced by DEN and DEN/CCl. In HCC cell lines, CMTM6 promoted cell proliferation and interacted with β-catenin, stabilizing it by preventing ubiquitination. In conclusion, our study suggested that CMTM6 upregulation promotes HCC cell proliferation through the β-catenin pathway, making it a potential therapeutic target for HCC treatment.

摘要

CMTM6 是 PD-L1 稳定性的调节剂，与多种癌症的发生发展有关。然而，CMTM6 在肝细胞癌（HCC）中的表达和作用仍存在争议。通过生物信息学分析和免疫荧光染色，我们的研究揭示了 CMTM6 表达与 HCC 预后之间的负相关关系。CMTM6 表达与甲胎蛋白（AFP）水平呈正相关，提示其可能作为 HCC 的预后标志物。利用 Cmtm6 基因敲除小鼠，我们发现 Cmtm6 缺失抑制 DEN 和 DEN/CCl 诱导的原发性肝癌模型中的 HCC 形成和细胞增殖。在 HCC 细胞系中，CMTM6 促进细胞增殖，并与 β-连环蛋白相互作用，通过阻止泛素化稳定其蛋白水平。综上所述，我们的研究表明，CMTM6 的上调通过 β-连环蛋白通路促进 HCC 细胞增殖，使其成为 HCC 治疗的潜在治疗靶点。