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    Branched actin relates cell migration with proliferation and cancer

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    SÉMINAIRE DE L'INSTITUT COCHIN


     

     

    Alexis Gautreau

    Ecole Polytechnique - Université Paris-Saclay - UMR7654 CNRS

     

    Lundi 16 octobre à 12H

     invité par Florence Niedergang

    Institut Cochin, 22 rue Méchain, 75014 Paris
    Salle de conférence Rosalind Franklin, 2e étage

    Abstract

    The actin cytoskeleton generates and senses forces. Signals that regulate cell proliferation are associated with actin-rich structures: membrane protrusions triggered by growth factors, cell adhesions to the extracellular matrix and to neighboring cells. Here we show that the specific pathway that generates cortical branched actin is critical for cell cycle progression. At the leading edge of migrating cells, ARPC1B-containing Arp2/3 complexes nucleate branched actin networks, which control G1 duration. Cortical branched actin integrates stimulation by soluble growth factors with signals mechano-transduced from cell adhesions, such as rigidity of the substratum and stretching of epithelial cells. Most cancer cells, which become independent from these biochemical and biophysical signals, have lost the requirement for cortical branched actin, but not tumour cells transformed by the RAC1 oncogene, which remain sensitive to Arp2/3 inhibition. The discovery of this novel actin checkpoint provides new diagnostic and therapeutic opportunities in cancer.

    The talk is fully devoted to an ongoing study, which is still unpublished. It is, however, based on the following previous publications of the group:

    • Molinie N, Gautreau A (2017). The Arp2/3 regulatory system and its deregulation in cancer. Physiol Rev. In press
    • Lomakina ME, […] Gautreau A (2016). Arpin down-regulation in breast cancer is associated with poor prognosis. Brit J Cancer. 114 :145-63.
    • Gorelik R, Gautreau A. (2015). The Arp2/3 inhibitory protein Arpin induces cell turning by pausing cell migration. Cytoskeleton 72:362-71.
    • Krause M, Gautreau A. (2014) Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nat Rev Mol Cell Biol. 15:577-90.
    • Dang I, Gorelik R, Sousa-Blin C, […] Gautreau A (2013) Inhibitory signalling to the Arp2/3 complex steers cell migration. Nature 503:281-4.


     

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