CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma
摘要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. <br> METHODS: CADM1 expression in HCC cell lines was mea-sured by quantitative real-time PCR. The function of CADM1 in the context of tumor suppression in HCC cells was deter-mined using proliferation assays, cell cycle analysis, EdU in-corporation assays,in vitro colony formation analysis, andin vivo tumorigenicity assays. The mechanism by which CADM1 acts as a tumor suppressor gene in HCC was investigated us-ing Western blotting analysis. <br> RESULTS: Downregulation of CADM1 expression is fre-quently detected in both HCC cells and clinical samples. Res-toration of CADM1 expression in HCC cell lines signiifcantly inhibits cell growth and negatively regulates the G1/S transi-tion. CADM1 overexpression can inhibit the tumorigenicity of HCC cells bothin vitro andin vivo. Western blotting analysis revealed that ectopic expression of CADM1 in HCC cells is associated with increased expression of Retinoblastoma (Rb) protein. <br> CONCLUSIONS: Our results showed that suppression of tu-morigenesis by CADM1 may be mediated by the Rb-E2F path-way, involving upregulation of Rb protein levels. This pathway could therefore represent an attractive target for HCC therapy.
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