Cancer Management and Research (Nov 2018)
ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer
Abstract
Xiong-Bo Guo,1,* Bin Huang,1,* Ying-Hua Pan,2 Shu-Guang Su,3 Yan Li3 1Department of General Surgery, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China; 2Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; 3Department of Pathology, The Affiliated Hexian Memorial Hospital of Southern Medical University, Guangzhou, China *These authors contributed equally to this work Background: Establishment 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.Methods: The 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.Results: In 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.Conclusion: Collectively, our data suggest that ESCO2 serves as a potential prognostic factor and exerts antimetastatic activity in CRC. Keywords: ESCO2, MMP2, EMT, metastasis, colorectal cancer
