2021
DOI: 10.1242/jcs.252957
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Fibronectin Extra Domains tune cellular responses and confer topographically distinct features to fibril networks

Abstract: Cellular fibronectin (FN) variants harboring one or two alternatively spliced Extra Domains (B and A) play a central bioregulatory role during development, repair processes and fibrosis. Yet, how the Extra Domains impact fibrillar assembly and function of the molecule remains unclear. Leveraging a unique biological toolset and image analysis pipeline for direct comparison of the variants, we demonstrate that the presence of one or both Extra Domains impacts FN assembly, function and physical properties of the … Show more

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Cited by 17 publications
(35 citation statements)
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“…During tumor progression, quiescent fibroblasts become activated by environmental cues that induce their phenotypic conversion from a “normal” to a “pro-tumoral” state (Fig 1A, top). This process is characterized by actin reorganization and increased contractility of cells that result in their elongation and the deposition of a highly anisotropic ECM (9). In vitro, these changes can be mimicked by treating normal fibroblasts with Transforming Growth Factor-β (TGF-β), a potent cytokine involved in fibroblast activation in the tumor microenvironment (9) (Fig 1A, bottom).…”
Section: Resultsmentioning
confidence: 99%
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“…During tumor progression, quiescent fibroblasts become activated by environmental cues that induce their phenotypic conversion from a “normal” to a “pro-tumoral” state (Fig 1A, top). This process is characterized by actin reorganization and increased contractility of cells that result in their elongation and the deposition of a highly anisotropic ECM (9). In vitro, these changes can be mimicked by treating normal fibroblasts with Transforming Growth Factor-β (TGF-β), a potent cytokine involved in fibroblast activation in the tumor microenvironment (9) (Fig 1A, bottom).…”
Section: Resultsmentioning
confidence: 99%
“…The presence of FN Extra Domains (EDA and/or EDB) impacts FN assembly and fibrillar network organization by normal fibroblasts (9). This was demonstrated by local analysis of graph-based features (i.e.…”
Section: Resultsmentioning
confidence: 99%
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“…108 EDB+ fibronectin in fibrils could enhance VEGF expression and phagocytosis. [109][110][111] EDB+/EDA+ fibronectin in fibrils could potently induce TGF-β mRNA expression, 112 which in turn, would create a positive feedback loop that further drives fibronectin expression. 104 Finally, the presence of EDA+ fibronectin in fibrils could enhance exposure of the RGD sequence in fibronectin 113 and hence binding to the α5β1 integrin, which would increase stress fibre formation and alter the contractile properties of TM cells.…”
Section: Fibronectinmentioning
confidence: 99%