Matrix metalloproteinase‑2 regulates MDA‑MB‑231 breast cancer cell invasion induced by active mammalian diaphanous-related formin 1

Mol Med Rep. 2016 Jul;14(1):277-82. doi: 10.3892/mmr.2016.5282. Epub 2016 May 13.

Abstract

Mammalian diaphanous‑related formin 1 (mDia1) was initially identified as a Rho GTPase effector involved in the progression of various diseases, including types of cancer. However, the precise underlying molecular mechanism of mDia1‑mediated cancer cell invasion remains to be elucidated. In the present study, mDia1 expression was demonstrated to be upregulated in tissues from a number of cancer types, including kidney, prostate, and breast cancer using immunohistochemical analysis. Forced expression of a constitutively active (CA) form of mDia1 induces invasion, as measured by Transwell invasion assay, of MDA‑MB‑231 cells, which is a highly invasive breast cancer cell line, and this effect was markedly impaired by matrix metalloproteinase (MMP)‑2 silencing. Furthermore, the present study demonstrated that overexpression of the CA form of mDia1 leads to the induction of invasive ability in MCF‑7 cells, which is a non‑invasive breast cancer cell line, as a result of increased MMP‑2 activity. Thus, the results of the current study suggest that mDia1 is an important regulator of breast cancer cell invasion and that this effect may be mediated by MMP‑2 activity.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Enzyme Activation
  • Female
  • Formins
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DIAPH1 protein, human
  • Formins
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9