Silencing of TMSG1 enhances metastasis capacity by targeting V-ATPase in breast cancer

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1312-20. eCollection 2015.


TMSG1, as a novel tumor metastasis suppressor gene, has been demonstrated to closely relate to the metastasis and drug-resistant of breast cancer. However, its molecular mechanism is still unclear. In this study, we explored the effect of small interference RNA (siRNA) targeting TMSG1 on the invasion of human breast carcinoma cell line MCF-7 and its molecular mechanisms associated with the extracellular pH. qRT-PCR and Western blot analysis revealed dramatic reduction of the levels of TMSG1 mRNA and protein after transfection of siRNA in MCF-7 cells. Cell migration and invasion were obviously increased by TMSG1 siRNA treatment. The activity of vacuolar ATPase (V-ATPase) and MMP-2 was significantly increased in MCF-7 cells transfected with the TMSG1 siRNA compared with the controls. Furthermore, acidic intracellular environment significantly increased the MMP-2 activity and the capacity of cell migration and invasion. In conclusion, silencing of TMSG1 increased V-ATPase activity, decreased extracellular pH and in turn the activation of secreted MMP-2, which ultimately promoted metastasis capacity of breast cancer cell.

Keywords: Breast cancer; MMP-2; TMSG1; V-ATPase; extracellular pH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydrogen-Ion Concentration
  • MCF-7 Cells
  • Matrix Metalloproteinase 2 / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • RNA Interference
  • RNA, Small Interfering
  • Sphingosine N-Acyltransferase / genetics*
  • Sphingosine N-Acyltransferase / metabolism
  • Transfection
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Vacuolar Proton-Translocating ATPases / metabolism*
  • Wound Healing / genetics


  • Membrane Proteins
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • CERS2 protein, human
  • Sphingosine N-Acyltransferase
  • Matrix Metalloproteinase 2
  • Vacuolar Proton-Translocating ATPases