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TMPRSS4 induces cancer cell invasion through pro-uPA processing

Hye-Jin Min1, Myung Kyu Lee2, Jung Weon Lee3

  • 1Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Republic of Korea.

Biochemical and Biophysical Research Communications
|January 18, 2014
PubMed

Insights

Transmembrane serine protease 4 (TMPRSS4) activates pro-urokinase-type plasminogen activator (pro-uPA), driving cancer invasion. This study reveals TMPRSS4

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • TMPRSS4 is a type II transmembrane serine protease highly expressed in various cancers, including pancreatic, thyroid, and colon.
  • Previous studies linked TMPRSS4 to cancer cell invasion, epithelial-mesenchymal transition, metastasis, and colorectal cancer progression.
  • TMPRSS4 was shown to upregulate urokinase-type plasminogen activator (uPA) gene expression, promoting cancer cell invasion.

Purpose of the Study:

  • To investigate the role of TMPRSS4's proteolytic activity in cancer cell invasion.
  • To determine if TMPRSS4 directly activates pro-uPA.
  • To elucidate the upstream regulatory mechanisms of pro-uPA activation by TMPRSS4.

Main Methods:

  • Analysis of conditioned medium from cells overexpressing TMPRSS4.
  • Assessing the association of the active TMPRSS4 protease domain with the plasma membrane.
  • Investigating the effect of TMPRSS4 on pro-uPA-mediated invasion in a serine proteolytic activity-dependent manner.

Main Results:

  • TMPRSS4 directly converts inactive pro-uPA into its active form via its proteolytic activity.
  • The active TMPRSS4 protease domain is released from cells and associates with the plasma membrane.
  • TMPRSS4 enhances pro-uPA-mediated invasion in a manner dependent on its serine proteolytic activity.

Conclusions:

  • TMPRSS4 acts as an upstream regulator of pro-uPA activation.
  • The proteolytic activity of TMPRSS4 is crucial for mediating cancer cell invasion.
  • This study provides key insights into the proteolytic function of TMPRSS4 and invasion control mechanisms.
Keywords:
InvasionProcessingTMPRSS4uPA

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