Supplementary Results from ERBB Receptor Activation Is Required for Profibrotic Responses to Transforming Growth Factor β
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posted on 2023-03-30, 19:49 authored by Mahefatiana Andrianifahanana, Mark C. Wilkes, Claire E. Repellin, Maryanne Edens, Theodore J. Kottom, Rod A. Rahimi, Edward B. LeofSupplementary Results from ERBB Receptor Activation Is Required for Profibrotic Responses to Transforming Growth Factor β
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ARTICLE ABSTRACT
Engagement of the transforming growth factor-β (TGF-β) receptor complex activates multiple signaling pathways that play crucial roles in both health and disease. TGF-β is a key regulator of fibrogenesis and cancer-associated desmoplasia; however, its exact mode of action in these pathologic processes has remained poorly defined. Here, we report a novel mechanism whereby signaling via members of the ERBB or epidermal growth factor family of receptors serves as a central requirement for the biological responses of fibroblasts to TGF-β. We show that TGF-β triggers upregulation of ERBB ligands and activation of cognate receptors via the canonical SMAD pathway in fibroblasts. Interestingly, activation of ERBB is commonly observed in a subset of fibroblast but not epithelial cells from different species, indicating cell type specificity. Moreover, using genetic and pharmacologic approaches, we show that ERBB activation by TGF-β is essential for the induction of fibroblast cell morphologic transformation and anchorage-independent growth. Together, these results uncover important aspects of TGF-β signaling that highlight the role of ERBB ligands/receptors as critical mediators in fibroblast responses to this pleiotropic cytokine. Cancer Res; 70(19); 7421–30. ©2010 AACR.Usage metrics
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