HEF1/Cas-L, A Novel Signal Transduction Molecule Associated with Cell Motility, Growth, Apoptosis and Oncogenic Transformation

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Developed by:

  • Erica A. Golemis, PhD

  • Background:

    The Cas family of docking proteins has been the subject of intense research because of its role in cell motility, growth, apoptosis and oncogenic transformation. These proteins are substrates of Focal Adhesion Kinase (FAK) and the Src family of tyrosine kinases—two active targets for drug development. Research at Fox Chase Cancer Center has shown that HEF1 protein production increases levels of mRNA transcripts that encode proteins associated with motility, cell transformation and invasiveness, including several metalloproteinases, MLCK, p160ROCK and ErbB2. HEF1 overproduction also mediates apoptosis in epithelial-derived cell lines, including MCF7 and HeLa cells. Recent clinical studies have found that overexpression of BCAR1 (p130Cas), a related protein, is associated with tamoxifen resistance. This highlights the importance of studying the role of this family of proteins in cancer prognosis. HEF1 is also the focus of research by investigators in immunology and other fields. HEF1 expression has been found to contribute to T cell migration induced by ligation of CD3 and α-integrin.

    Description:

    Dr. Erica Golemis and colleagues of Fox Chase Cancer Center have discovered and characterized HEF1/Cas-L (Human Enhancer of Filamentation 1), a member of the Cas family of docking proteins that also includes p130Cas and Efs/Sin. HEF-1 is a multifunctional protein involved in integrin-based signaling that affects cell motility, growth, apoptosis and oncogenic transformation. U.S. patents have been granted that broadly cover HEF-1; Foreign counterparts are pending. Fox Chase Cancer Center is offering licenses to HEF-1 cell lines, antibodies, reagents and patents for both research and commercial uses.

    Applications:

    • Cancer
    • α-Integrin-mediated processes
    • Inflammation and Immunology

    Opportunity:

    Both research use and commercial licenses are available
    • Rabbit polyclonal antibodies specific for HEF1, with no cross-reactivity to p130Cas or Efs/Sin
    • Cell lines in which HEF1 production is regulated by an inducible promoter
    • A variety of other cell lines and reagents useful in defining the effect of drug candidates on HEF1 expression, and in differentiating between HEF1 and p130Cas effects.

    Publications:

    • Fashena, S.J. et al., "Dissection of HEF1-dependent functions in motility and transcriptional regulation," J. Cell Sci 115: 99-111
    • Law, SF et al., "The docking protein HEF1 is an apoptotic mediator at focal adhesion sites," J. Immunol. 163:3727-3734
    • Van Seventer, GA et al., "Focal adhesion kinase regulates α-integrin dependent migration through an HEF1 effector pathway," Eur. J. Immunol. 31: 1417-1427

    Patent Status:

    U.S. patent 5,716,782: Nucleic Acid Encoding A signal Mediator Protein that Induces Morphological Change
    U.S. 6,124,434: Signal Mediator Protein That Induces Morphological Alterations.
    U.S. 6,100,384: Antibodies Immunologically Specific for a Signal Mediator Protein that Induces Cellular Morphological Alterations.
    Australian patent 715,537: Nucleic Acid Encoding a Signal Mediator Protein that Induces Cellular Morphological Alterations
    • Additional foreign patent applications have been filed.

    For licensing information, contact

    Clarissa Ceruti, PhD, MBA
    Fox Chase Cancer Center
    610 Old York Road, Suite 400
    Room 407
    Jenkintown, PA 19046
    Tel.: 617-792-6521
    Fax: 215-214-1440
    clarissa.ceruti@fccc.edu