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Localization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells

Guangli Wang1, Yao Zeng1, Shaoying Chen1

  • 1Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province, 515041, China.

Scientific Reports
|October 21, 2017
PubMed

Insights

Tissue factor pathway inhibitor-2 (TFPI-2) suppresses breast cancer growth and invasion. Nuclear TFPI-2 inhibits MMP-2 gene transcription by interacting with Ap-2α, reducing breast cancer cell invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tissue factor pathway inhibitor-2 (TFPI-2) is recognized as a tumor suppressor.
  • TFPI-2 modulates extracellular matrix (ECM) integrity and regulates oncogenes.

Purpose of the Study:

  • To investigate the mechanism of TFPI-2 in suppressing breast cancer growth and invasion.
  • To elucidate the role of nuclear TFPI-2 in regulating gene transcription.

Main Methods:

  • Over-expression of TFPI-2 in breast cancer cells.
  • Treatment with exogenous recombinant TFPI-2 (rTFPI-2).
  • Analysis of TFPI-2 cellular localization, MMP-2 mRNA expression, and TFPI-2/Ap-2α interaction with the MMP-2 promoter.

Main Results:

  • TFPI-2 over-expression or rTFPI-2 treatment reduced breast cancer cell proliferation and invasion.
  • TFPI-2 was found in the cytoplasm and nucleus.
  • Nuclear TFPI-2 inhibited MMP-2 mRNA expression and transcriptional activity by interacting with Ap-2α and attenuating its binding to the MMP-2 promoter.

Conclusions:

  • TFPI-2 suppresses breast cancer cell invasion.
  • Nuclear localization of TFPI-2 is crucial for inhibiting MMP-2 gene transcription.
  • TFPI-2 acts as a tumor suppressor by regulating MMP-2 transcription via nuclear mechanisms.

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