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Updated: Apr 15, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Fibulin-3 is a novel TGF-β pathway inhibitor in the breast cancer microenvironment

H Tian1, J Liu2,3, J Chen1

  • 1Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.

Oncogene
|March 31, 2015
PubMed

Insights

Fibulin-3, a novel protein, inhibits transforming growth factor-β (TGF-β) signaling in breast cancer. Decreased fibulin-3 levels correlate with poorer prognosis, suggesting its therapeutic potential in breast cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor-β (TGF-β) is a key regulator of breast cancer progression.
  • The role of the tumor microenvironment in modulating TGF-β signaling is not fully understood.

Purpose of the Study:

  • To identify microenvironmental factors regulating TGF-β signaling in breast cancer.
  • To elucidate the mechanism of fibulin-3's action and its clinical relevance.

Main Methods:

  • Identification of fibulin-3 as a secreted protein affecting TGF-β signaling.
  • Investigation of fibulin-3's interaction with TGF-β receptors (TβRI and TβRII).
  • Assessment of fibulin-3's functional impact on TGF-β-mediated processes in vitro and in vivo.

Main Results:

  • Fibulin-3 inhibits TGF-β signaling by blocking TβRI/TβRII complex formation.
  • Reduced fibulin-3 expression correlates with advanced breast cancer and poor prognosis.
  • Fibulin-3 suppresses TGF-β-induced epithelial-mesenchymal transition (EMT), migration, invasion, and endothelial permeability.
  • Restoring fibulin-3 inhibits breast cancer progression and metastasis in vivo.

Conclusions:

  • Fibulin-3 is a novel tumor suppressor that inhibits TGF-β signaling within the breast cancer microenvironment.
  • Fibulin-3's expression level is a prognostic biomarker for breast cancer.
  • Targeting fibulin-3 or the TGF-β pathway presents a potential therapeutic strategy for breast cancer.

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