Targeting Src in endometriosis-associated ovarian cancer

Manek, R., Pakzamir, E., Mhawech-Fauceglia, P., Pejovic, T., Sowter, H. ORCID: 0000-0002-1408-1900, Gayther, S. and Lawrenson, K., 2016. Targeting Src in endometriosis-associated ovarian cancer. Oncogenesis, 5 (8): e251. ISSN 2157-9024

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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.

Item Type: Journal article
Publication Title: Oncogenesis
Creators: Manek, R., Pakzamir, E., Mhawech-Fauceglia, P., Pejovic, T., Sowter, H., Gayther, S. and Lawrenson, K.
Publisher: Springer
Date: 2016
Volume: 5
Number: 8
ISSN: 2157-9024
Identifiers:
NumberType
10.1038/oncsis.2016.54DOI
1205352Other
Rights: Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 25 Nov 2019 10:53
Last Modified: 01 May 2020 09:01
URI: http://irep.ntu.ac.uk/id/eprint/38473

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