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Updated: Sep 27, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

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

Published on: October 27, 2020

TACE is required for the activation of the EGFR by TGF-alpha in tumors

Maria Borrell-Pagès1, Federico Rojo, Joan Albanell

  • 1Laboratori de Recerca Oncològica, Servei d'Oncologia Medica, Hospital Universitari Vall d'Hebron, Psg Vall d'Hebron 119-129, Barcelona 08035, Spain.

The EMBO Journal
|February 28, 2003
PubMed

Insights

Tumor necrosis factor-alpha converting enzyme (TACE) shedding of pro-transforming growth factor-alpha (proTGF-alpha) is crucial for epidermal growth factor receptor (EGFR) activation and tumor development. TACE overexpression in mammary tumors suggests it as a promising anti-cancer therapeutic target.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell signaling

Background:

  • Intracellular signaling pathways of epidermal growth factor receptor (EGFR) are well-understood and targeted in cancer therapy.
  • Mechanisms initiating receptor activation signals remain less clear.

Purpose of the Study:

  • To investigate the role of transforming growth factor-alpha (TGF-alpha) shedding in EGFR activation.
  • To determine the involvement of tumor necrosis factor-alpha converting enzyme (TACE) in EGFR signaling and tumorigenesis.

Main Methods:

  • Studied the interaction between transmembrane pro-transforming growth factor-alpha (proTGF-alpha) and EGFR when shedding is inhibited.
  • Assessed the requirement of TACE activity for EGFR activation in vivo.
  • Analyzed TACE expression in mammary tumors.

Main Results:

  • Preventing proTGF-alpha shedding results in interaction with, but not activation of, EGFR.
  • TACE activity is essential for EGFR activation in vivo and tumor formation in mice.
  • TACE is significantly overexpressed in most analyzed mammary tumors.

Conclusions:

  • Proteolytic shedding of proTGF-alpha by TACE is a critical regulatory step for EGFR activation.
  • TACE plays a crucial role in tumorigenesis and represents a potential therapeutic target for anti-cancer strategies.

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