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Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vascular invasion. Patients with elevated expression of CBX1 were frequently accompanied with unfavorable overall and disease-free survivals in two independent cohorts consisting of 648 HCC cases. The prognostic value of CBX1 was further confirmed by stratified survival analyses. Multivariate cox regression model suggested CBX1 as an independent factor for overall survival (hazard ratio = 1.735, 95% confident interval: 1.342–2.244, P < .001). In vitro data demonstrated that CBX1 overexpression promoted cell proliferation and migration, whereas the knockdown of CBX1 resulted in the opposite phenotypes. Mechanistically, CBX1 interacted with transcription factor HMGA2 to activate the Wnt/β-Catenin signaling pathway. Suppression of β-Catenin by siRNA or specific inhibitor XAV-939 markedly attenuated CBX1-mediated cell growth. Collectively, our findings indicate that CBX1 functions as an oncogene and may serve as a potential prognostic biomarker in HCC.

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BackgroundEstablishment of cohesion 1 homolog 2 (ESCO2) plays important roles in the regulation of cohesion and genomic stability and has been implicated in human cancers. Yet, its clinical significance and biological function in colorectal cancer (CRC) are unknown.MethodsThe expression of ESCO2 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of ESCO2 in the tumor metastasis of CRC and the related mechanisms were investigated using in vitro and in vivo models.ResultsIn this study, we show that low expression of ESCO2 in CRC was closely correlated with lymphatic and distant metastasis. Patients with low ESCO2 expression experienced shorter overall survival and disease-free survival in two independent cohorts containing a total of 587 CRC cases. ESCO2 overexpression suppressed, whereas ESCO2 knockdown promoted cell migration in vitro and tumor metastasis in vivo via modulation of epithelial–mesenchymal transition (EMT) process. Mechanistically, ESCO2 inhibited the transcriptional activity of MMP2 promoter to downregulate its expression. Reexpression of MMP2 partially attenuated the ESCO2-mediated malignant phenotypes.ConclusionCollectively, our data suggest that ESCO2 serves as a potential prognostic factor and exerts antimetastatic activity in CRC.

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