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    Targeting Src in endometriosis-associated ovarian cancer

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    Authors
    Manek, Roxanne
    Pakzamir, Elham
    Mhawech-Fauceglia, Paulette
    Pejovic, Tanja
    Sowter, Heidi M. cc
    Gayther, Simon A.
    Lawrenson, Kate
    Affiliation
    University of Southern California
    Oregon Health and Science University
    University of Derby
    Samuel Oschin Comprehensive Cancer Institute
    Issue Date
    2016-08-15
    
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    Abstract
    The SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416.
    Citation
    Manek, R. et al (2016) 'Targeting Src in endometriosis-associated ovarian cancer' Oncogenesis, 5 (8):e251
    Publisher
    Nature
    Journal
    Oncogenesis
    URI
    http://hdl.handle.net/10545/621543
    DOI
    10.1038/oncsis.2016.54
    Additional Links
    http://www.nature.com/doifinder/10.1038/oncsis.2016.54
    Type
    Article
    Language
    en
    ISSN
    21579024
    ae974a485f413a2113503eed53cd6c53
    10.1038/oncsis.2016.54
    Scopus Count
    Collections
    School of Environmental Sciences

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