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Differential regulation of fibronectin expression and fibrillogenesis by autocrine TGF-ß1 signaling in malignant and benign mammary epithelial cells.
Sofroniou, Michael M; Lemmon, Christopher A.
Afiliação
  • Sofroniou MM; Department of Biomedical Engineering, Virginia Commonwealth University, 410 West Main St., Richmond, VA 23284, USA.
  • Lemmon CA; Department of Biomedical Engineering, Virginia Commonwealth University, 410 West Main St., Richmond, VA 23284, USA. Electronic address: clemmon@vcu.edu.
Int J Biochem Cell Biol ; 165: 106478, 2023 Dec.
Article em En | MEDLINE | ID: mdl-37866655
Remodeling of the extracellular matrix (ECM) is a key hallmark of cancer progression. A critical component of ECM remodeling is the assembly of the glycoprotein fibronectin (FN) into insoluble fibrils, which provide a scaffold for invading vascular endothelial cells and escaping cancer cells, as well as a framework for collagen deposition and oncogenic cytokine tethering. FN fibril assembly is induced by Transforming Growth Factor-ß1 (TGF-ß1), which was originally identified for its role in malignant transformation. Addition of exogenous TGF-ß1 drives FN fibril assembly while also upregulating endogenous TGF-ß1 expression and autocrine signaling. In the current study, we sought to determine if autocrine TGF-ß1 signaling plays a role in FN fibril formation in either MCF10A mammary epithelial cells, which behave similarly to healthy epithelia, or malignant MDA- MB-231 breast cancer cells. Our results show two interesting findings: first, malignant MDA-MB- 231 cells assemble less FN into fibrils, despite expressing and secreting more soluble FN; second, autocrine TGF-ß1 signaling is required for FN fibril formation in MCF10A epithelial cells, even in the presence of exogenous, active TGF-ß1. This suggests that autocrine TGF-ß1 is signaling through distinct pathways from active exogenous TGF-ß1. We hypothesized that this signaling was mediated by interactions between the TGF-ß1 latency associated peptide (LAP) and αv integrins; indeed, incubating MCF10As with soluble LAP, even in the absence of the active TGF-ß1 ligand, partially recovered FN fibril assembly. Taken together, these data suggests that autocrine TGF-ß1 plays a critical role in FN fibril assembly, and this interaction is mediated by LAP-integrin signaling.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Fibronectinas / Fator de Crescimento Transformador beta1 Idioma: En Revista: Int J Biochem Cell Biol Assunto da revista: BIOQUIMICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Fibronectinas / Fator de Crescimento Transformador beta1 Idioma: En Revista: Int J Biochem Cell Biol Assunto da revista: BIOQUIMICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos