Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-06

AUTHORS

Fernando Calvo, Nil Ege, Araceli Grande-Garcia, Steven Hooper, Robert P. Jenkins, Shahid I. Chaudhry, Kevin Harrington, Peter Williamson, Emad Moeendarbary, Guillaume Charras, Erik Sahai

ABSTRACT

To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed their function and gene expression. These analyses reveal that activation of the YAP transcription factor is a signature feature of CAFs. YAP function is required for CAFs to promote matrix stiffening, cancer cell invasion and angiogenesis. Remodelling of the ECM and promotion of cancer cell invasion requires the actomyosin cytoskeleton. YAP regulates the expression of several cytoskeletal regulators, including ANLN and DIAPH3, and controls the protein levels of MYL9 (also known as MLC2). Matrix stiffening further enhances YAP activation, thus establishing a feed-forward self-reinforcing loop that helps to maintain the CAF phenotype. Actomyosin contractility and Src function are required for YAP activation by stiff matrices. Further, transient ROCK inhibition is able to disrupt the feed-forward loop, leading to a long-lasting reversion of the CAF phenotype. More... »

PAGES

637

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncb2756

    DOI

    http://dx.doi.org/10.1038/ncb2756

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004671181

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23708000


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