AKIMASA ICHINOE    Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer
Journal	Formal name：Oncogene Abbreviation：Oncogene ISSN code：09509232/14765594
Domestic / Foregin	Foregin
Volume, Issue, Page	35,pp.4471-4480
Total page number	10
Author and coauthor	H Yagi†, K Asanoma, T Ohgami, A Ichinoe, K Sonoda, K Kato
Publication date	2016
Summary	G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. Gα12 and Gα13, encoded by GNA12 and GNA13, respectively, are referred to as the GEP oncogene and are implicated in tumor progression. However, the molecular mechanisms by which Gα12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of Gα12/13 in human ovarian cancer tissues. Gα12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, Gα12/13 activation promoted cell growth. We used a synthetic biology approach using chimeric G proteins and GPCRs activated solely by artificial ligands to selectively trigger signaling pathways downstream of specific G proteins. We found that Gα12/13 promotes proliferation of ovarian cancer cells by activating the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway. Furthermore, we reveal that inhibition of YAP by short hairpin RNA or a specific inhibitor prevented the growth of ovarian cancer cells. Therefore, YAP may be a suitable therapeutic target in ovarian cancer.