Targeting Src in endometriosis-associated ovarian cancer

Journal article


Manek, Roxanne, Pakzamir, Elham, Mhawech-Fauceglia, Paulette, Pejovic, Tanja, Sowter, Heidi M., Gayther, Simon A. and Lawrenson, Kate 2016. Targeting Src in endometriosis-associated ovarian cancer. Oncogenesis. https://doi.org/10.1038/oncsis.2016.54
AuthorsManek, Roxanne, Pakzamir, Elham, Mhawech-Fauceglia, Paulette, Pejovic, Tanja, Sowter, Heidi M., Gayther, Simon A. and Lawrenson, Kate
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.

KeywordsOvarian cancer; SRC proto-oncogene; Oncology; Cancer treatment
Year2016
JournalOncogenesis
PublisherNature
ISSN21579024
Digital Object Identifier (DOI)https://doi.org/10.1038/oncsis.2016.54
Web address (URL)http://hdl.handle.net/10545/621543
hdl:10545/621543
Publication dates15 Aug 2016
Publication process dates
Deposited13 Apr 2017, 09:14
Accepted20 Jun 2016
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Archived with thanks to Oncogenesis

ContributorsUniversity of Southern California, Oregon Health and Science University, University of Derby and Samuel Oschin Comprehensive Cancer Institute
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