Name:
oncogenesis 2016.pdf
Size:
2.680Mb
Format:
PDF
Description:
Published PDF (Open Access CCBY)
Authors
Manek, RoxannePakzamir, Elham
Mhawech-Fauceglia, Paulette
Pejovic, Tanja
Sowter, Heidi M.

Gayther, Simon A.
Lawrenson, Kate
Affiliation
University of Southern CaliforniaOregon Health and Science University
University of Derby
Samuel Oschin Comprehensive Cancer Institute
Issue Date
2016-08-15
Metadata
Show full item recordAbstract
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):e251Publisher
NatureJournal
OncogenesisDOI
10.1038/oncsis.2016.54Additional Links
http://www.nature.com/doifinder/10.1038/oncsis.2016.54Type
ArticleLanguage
enISSN
21579024ae974a485f413a2113503eed53cd6c53
10.1038/oncsis.2016.54