UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI, Harrington K, Williamson P, Moeendarbary E, Charras G, Sahai E
  • Publication date:
    06/2013
  • Pagination:
    637, 646
  • Journal:
    Nat Cell Biol
  • Volume:
    15
  • Issue:
    6
  • Status:
    Published
  • Country:
    England
  • PII:
    ncb2756
  • Language:
    eng
  • Keywords:
    Actin Cytoskeleton, Actomyosin, Adaptor Proteins, Signal Transducing, Animals, Breast Neoplasms, Cell Cycle Proteins, Cells, Cultured, Disease Progression, Enzyme Activation, Extracellular Matrix, Female, Fibroblasts, Focal Adhesions, Humans, Mechanotransduction, Cellular, Mice, Microscopy, Atomic Force, Microtubule-Associated Proteins, Myosin Light Chains, NADPH Dehydrogenase, Neoplasm Invasiveness, Neovascularization, Pathologic, Phosphoproteins, Phosphorylation, RNA Interference, RNA, Small Interfering, rho-Associated Kinases, src-Family Kinases
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.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
London Centre for Nanotechnology
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by