イチノエ　アキマサ   AKIMASA ICHINOE   一戸　晶元    所属   医学部 医学科（附属足立医療センター）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer
掲載誌名	正式名：Oncogene 略　 称：Oncogene ISSNコード：09509232/14765594
掲載区分	国外
巻・号・頁	35,pp.4471-4480
総ページ数	10
著者・共著者	H Yagi†, K Asanoma, T Ohgami, A Ichinoe, K Sonoda, K Kato
発行年月	2016
概要	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.