CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma
CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma
复制标题
CADM1通过Rb-E2F通路调节肝细胞癌的G1/S转变并抑制致瘤性
DOI：
10.1016/s1499-3872(16)60099-1
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发表时间：
2016-06-01
影响因子：
3.3
通讯作者：
Zheng, Shu-Sen
中科院分区：
文献类型：
--
作者：
Zhang, Wu;Xie, Hai-Yang;Zheng, Shu-Sen
背景：越来越多的证据表明，细胞粘附分子1（CADM 1）的下调有助于各种癌症的肿瘤发生。本研究旨在探讨CADM 1在人肝细胞癌（HCC）中的表达模式，并探讨CADM 1介导的肿瘤抑制机制。使用增殖测定、细胞周期分析、EdU掺入测定、体外集落形成分析和体内致瘤性测定来确定CADM 1在HCC细胞中肿瘤抑制背景下的功能。结果：CADM 1在肝癌细胞和临床标本中均表达下调。肝癌细胞系中CADM 1表达的恢复显著抑制细胞生长并负调节G1/S转换。CADM 1过表达可抑制肝癌细胞在体内外的致瘤性。Western blotting分析显示，肝癌细胞中CADM 1的异位表达与视网膜母细胞瘤（Retinoblastoma，Rb）蛋白的表达增加有关。结论：我们的研究结果表明，CADM 1抑制肿瘤发生可能是由Rb-E2 F通路介导的，涉及Rb蛋白水平的上调。因此，该途径可能是HCC治疗的一个有吸引力的靶点。
BACKGROUND: Increasing evidence indicates that down regulation of cell adhesion molecule 1 (CADM1) contributes to tumorigenesis in various cancers. The present study was undertaken to investigate the CADM1 expression pattern in human hepatocellular carcinoma (HCC), and to elucidate the mechanism underlying CADM1-mediated tumor suppression.METHODS: CADM1 expression in HCC cell lines was measured by quantitative real-time PCR. The function of CADM1 in the context of tumor suppression in HCC cells was determined using proliferation assays, cell cycle analysis, EdU incorporation assays, in vitro colony formation analysis, and in vivo tumorigenicity assays. The mechanism by which CADM1 acts as a tumor suppressor gene in HCC was investigated using Western blotting analysis.RESULTS: Downregulation of CADM1 expression is frequently detected in both HCC cells and clinical samples. Restoration of CADM1 expression in HCC cell lines significantly inhibits cell growth and negatively regulates the G1/S transition. CADM1 overexpression can inhibit the tumorigenicity of HCC cells both in vitro and in vivo. Western blotting analysis revealed that ectopic expression of CADM1 in HCC cells is associated with increased expression of Retinoblastoma (Rb) protein.CONCLUSIONS: Our results showed that suppression of tumorigenesis by CADM1 may be mediated by the Rb-E2F pathway, involving upregulation of Rb protein levels. This pathway could therefore represent an attractive target for HCC therapy.