MDC1 promotes ovarian cancer metastasis by inducing epithelial-mesenchymal transition
- 411 Downloads
Ovarian cancer is a highly invasive cancer with poor prognosis. Previous studies have revealed lots of connections between the invasiveness and epithelial-mesenchymal transition (EMT), which is common during the progression of ovarian cancer. MDC1, a mediator of DNA damage checkpoint, has recently been implicated as a potential oncogene. Here, in this article, we studied the role of MDC1 in ovarian cancer metastasis. First, in tissue samples, we found that high expression level of MDC1 was correlated with poor prognosis. Furthermore, MDC1 overexpression in ovarian cancer cells significantly increased migration and invasion. In contrast, silencing MDC1 reversed these processes. Consistently, nude mice xenograft confirmed that silencing MDC1 suppressed tumor metastasis in vivo. We further demonstrated that MDC1 induced EMT through modulation EMT markers such as E-cadherin, N-cadherin, and vimentin. Taken together, our findings suggest that MDC1 promotes ovarian cancer metastasis through the induction of EMT.
KeywordsMDC1 Metastasis EMT Ovarian cancer
This study was supported by the National 863 Program (2014AA020605) and the National Natural Science Foundation of China (81272857, 81171897).
Conflicts of interest
- 22.Ye Q, Chen L, Yin X, Liu YJ, Ji Q, Zhao E: Development of serous ovarian cancer is associated with the expression of homologous recombination pathway proteins. Pathology oncology research. POR. 2014.Google Scholar
- 27.Goodwin JF, Knudsen KE: Beyond DNA repair: DNA-pk function in cancer. Cancer discovery. 2014.Google Scholar
- 31.Bartkova J, Horejsi Z, Sehested M, Nesland JM, Rajpert-De Meyts E, Skakkebaek NE, et al. DNA damage response mediators mdc1 and 53 bp1: Constitutive activation and aberrant loss in breast and lung cancer, but not in testicular germ cell tumours. Oncogene. 2007;26:7414–22.CrossRefPubMedGoogle Scholar