Work

Identification and targeting of a TACE-dependent autocrine loop which predicts poor prognosis in breast cancer

Year: 2005

Type: article

Abstract: The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop which provides an oncogenic stimulus in the absence of proto-oncogene mutation. Inhibition of this protease, TACE/ADAM17, reverts the malignant phenotype by preventing mobilization of two crucial growth factors, Amphiregulin and TGF{alpha}. We show further that the efficacy of EGFR inhibitors is overcome by physiological levels of growth factors and that successful EGFR inhibition is dependent on reducing ligand bioavailability. Using existing patient outcome data, we demonstrate a strong correlation between TACE and TGF{alpha} expression in human breast cancers that is predictive of poor prognosis.

Source: University of North Texas Digital Library (University of North Texas)

Authors: Paraic A. Kenny, Mina J. Bissell

Language: English

Topic: Protease and Inhibitor Mechanisms

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: U.S. Department of Defense, U.S. Department of Energy, National Cancer Institute, Biological and Environmental Research

Award: G1398330795

OpenAlex ID: W2336521123

FWCI:

Cites: 44

Cited by:

Related to: 10