TY - JOUR
T1 - GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer
AU - Yagi, H.
AU - Asanoma, K.
AU - Ohgami, T.
AU - Ichinoe, A.
AU - Sonoda, K.
AU - Kato, K.
N1 - Funding Information:
We are grateful to Ms Emiko Hori, Ms Yoko Miyanari and Research Support Center, Graduate School of Medical Science, Kyushu University for technical supports. This study was supported in part by a Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#24791709 and #26861332).
Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2016/8/25
Y1 - 2016/8/25
N2 - G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. G12 and G13, 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 G12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of G12/13 in human ovarian cancer tissues. G12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, G12/13 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 G12/13 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.
AB - G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. G12 and G13, 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 G12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of G12/13 in human ovarian cancer tissues. G12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, G12/13 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 G12/13 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.
UR - http://www.scopus.com/inward/record.url?scp=84955575790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955575790&partnerID=8YFLogxK
U2 - 10.1038/onc.2015.505
DO - 10.1038/onc.2015.505
M3 - Article
C2 - 26804165
AN - SCOPUS:84955575790
SN - 0950-9232
VL - 35
SP - 4471
EP - 4480
JO - Oncogene
JF - Oncogene
IS - 34
ER -
