TFPI inhibits breast cancer progression by suppressing ERK/p38 MAPK signaling pathway

Mengying Xing1, Ying Yang1, Jiaxue Huang1

  • 1Department of Medical Genetics, School of Basic Medical Sciences, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, People's Republic of China.

Genes & Genomics
|May 14, 2022
PubMed
Abstract

Insights

Tissue factor pathway inhibitor-1 (TFPI) is downregulated in breast cancer, correlating with worse survival. TFPI inhibits cancer cell proliferation, migration, and invasion by affecting the ERK/p38 MAPK pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tissue factor pathway inhibitor-1 (TFPI) is a key regulator of coagulation.
  • Emerging evidence suggests TFPI possesses antitumor properties.
  • TFPI expression is often reduced in various cancer types.

Purpose of the Study:

  • To investigate the role of TFPI in breast cancer.
  • To elucidate the molecular mechanisms underlying TFPI's function in breast cancer.
  • To assess TFPI as a potential prognostic biomarker and therapeutic target.

Main Methods:

  • Bioinformatic analysis using UALCAN and Kaplan-Meier plotter.
  • Immunohistochemistry and Western blot for TFPI expression.
  • Cell proliferation, migration, and invasion assays (CCK-8, colony formation, transwell).
  • Methylation-specific PCR to assess promoter methylation.

Main Results:

  • TFPI expression is significantly decreased in breast cancer tissues and cells.
  • Low TFPI levels correlate with poorer overall survival.
  • TFPI overexpression inhibits, while knockdown promotes, breast cancer cell proliferation, migration, and invasion.
  • TFPI acts by inhibiting the ERK/p38 MAPK signaling pathway.
  • DNA hypermethylation of the TFPI promoter contributes to its downregulation.

Conclusions:

  • TFPI suppresses breast cancer progression by inhibiting the ERK/p38 MAPK pathway.
  • TFPI demonstrates potential as a prognostic biomarker for breast cancer.
  • TFPI represents a promising therapeutic target for breast cancer treatment.

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