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• W2097431319 endingPage "7430" @default.
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• W2097431319 abstract "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." @default.
• W2097431319 created "2016-06-24" @default.
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• W2097431319 date "2010-09-29" @default.
• W2097431319 modified "2023-10-02" @default.
• W2097431319 title "ERBB Receptor Activation Is Required for Profibrotic Responses to Transforming Growth Factor β" @default.
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• W2097431319 doi "https://doi.org/10.1158/0008-5472.can-10-0232" @default.
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