MDC1 promotes ovarian cancer metastasis by inducing epithelial-mesenchymal transition

Tumour Biol. 2015 Jun;36(6):4261-9. doi: 10.1007/s13277-015-3063-5. Epub 2015 Jan 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • RNA, Small Interfering
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Vimentin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Cell Cycle Proteins
  • MDC1 protein, human
  • Nuclear Proteins
  • RNA, Small Interfering
  • Trans-Activators
  • Vimentin