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The role of thrombomodulin in modulating ITGB3 expression and its implications for triple-negative breast cancer

Yu-Jia Chang1,2,3,4, G M Shazzad Hossain Prince1, Po-Li Wei4,5,6,7

  • 1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Cell Biology International
|December 11, 2023
PubMed

Insights

Thrombomodulin (TM) regulates Integrin beta 3 (ITGB3) in triple-negative breast cancer (TNBC). TM suppresses TNBC growth and metastasis by reducing ITGB3, a marker of poor survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective therapies.
  • Thrombomodulin (TM) is implicated in various cancers, but its role in TNBC is unclear.
  • Identifying novel therapeutic targets and biomarkers for TNBC is critical.

Purpose of the Study:

  • To investigate the role of Thrombomodulin (TM) in triple-negative breast cancer (TNBC).
  • To elucidate the regulatory relationship between TM and Integrin beta 3 (ITGB3) in TNBC.
  • To assess the potential of TM and ITGB3 as biomarkers or therapeutic targets in TNBC.

Main Methods:

  • Manipulating TM expression (silencing and overexpression) in TNBC cell lines (MDA-MB-231, Hs578T).
  • Assessing cell proliferation, invasion, and migration.
  • Utilizing RNA-sequencing (RNA-seq), quantitative PCR (qPCR), and Western blot analysis.
  • Investigating the involvement of the smad2/3 pathway.
  • Correlating ITGB3 levels with patient survival data.

Main Results:

  • Silencing TM increased proliferation and metastasis; overexpressing TM reduced these.
  • TM negatively regulates Integrin beta 3 (ITGB3) expression via the smad2/3 pathway.
  • Silencing ITGB3 in TM-silenced cells decreased proliferation and migration.
  • High ITGB3 levels correlate with poor overall and relapse-free survival in TNBC patients.

Conclusions:

  • Thrombomodulin (TM) acts as a tumor suppressor in triple-negative breast cancer (TNBC).
  • TM negatively regulates Integrin beta 3 (ITGB3), a key driver of TNBC progression.
  • ITGB3 is a potential prognostic biomarker and therapeutic target for TNBC.
Keywords:
ITGB3TNBCbreast cancerproliferationsmad2/3thrombomodulin

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