Survivin promotes the invasion of human colon carcinoma cells by regulating the expression of MMP‑7

Mol Med Rep. 2014 Mar;9(3):825-30. doi: 10.3892/mmr.2014.1897. Epub 2014 Jan 14.

Abstract

Increased expression levels of survivin are crucial for invasion activity in several types of human cancer, including colon carcinoma. However, the molecular mechanisms whereby survivin regulates cancer invasion have not been completely elucidated. To the best of our knowledge, this study is the first to investigate the role of matrix metalloprotease‑7 (MMP‑7) in cell invasion that is induced by survivin by using in vitro assays, including western blot, immunofluorescence and qPCR analyses. The results demonstrated that the ectopic expression of survivin significantly promoted the invasive activity of colon carcinoma cells (SW620 and HCT‑116) and resulted in increased levels of MMP‑7 activation. By contrast, the small interfering RNA (siRNA)‑based knockdown of survivin markedly reduced cell migration and led to a dose‑dependent decrease in MMP‑7 expression levels. Compared with the controls, knockdown of MMP‑7 by siRNA in colon carcinoma cells led to reduced invasion ability, whereas no obvious changes were observed when MMP‑7 expression was silenced in survivin‑overexpressing colon carcinoma cells. These findings demonstrate that MMP‑7 is crucial for survivin‑mediated invasiveness, suggesting that the survivin‑mediated MMP‑7 signaling pathway is a potential therapeutic target for the treatment of colon carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Matrix Metalloproteinase 7 / chemistry
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Survivin
  • Up-Regulation

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • RNA, Small Interfering
  • Survivin
  • Matrix Metalloproteinase 7