@article{eef31b848c3b462d92b0bf0e6d6cd8ec,
title = "Growth hormone-releasing hormone receptor antagonists inhibit human gastric cancer through downregulation of PAK1-STAT3/NF-κB signaling",
abstract = "Gastric cancer (GC) ranks as the fourth most frequent in incidence and second in mortality among all cancers worldwide. The development of effective treatment approaches is an urgent requirement. Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) have been found to be present in a variety of tumoral tissues and cell lines. Therefore the inhibition of GHRH-R was proposed as a promising approach for the treatment of these cancers. However, little is known about GHRH-R and the relevant therapy in human GC. By survival analyses of multiple cohorts of GC patients, we identified that increased GHRH-R in tumor specimens correlates with poor survival and is an independent predictor of patient prognosis. We next showed that MIA-602, a highly potent GHRH-R antagonist, effectively inhibited GC growth in cultured cells. Further, this inhibitory effect was verified in multiple models of human GC cell lines xenografted into nude mice. Mechanistically, GHRH-R antagonists target GHRH-R and down-regulate the p21-activated kinase 1 (PAK1)-mediated signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB) inflammatory pathway. Overall, our studies establish GHRH-R as a potential molecular target in human GC and suggest treatment with GHRH-R antagonist as a promising therapeutic intervention for this cancer.",
keywords = "GHRH receptor, GHRH-R antagonist, PAK1, Prognostic predictor, Stomach cancer",
author = "Jinfeng Gan and Xiurong Ke and Jiali Jiang and Hongmei Dong and Zhimeng Yao and Yusheng Lin and Wan Lin and Xiao Wu and Shumei Yan and Yixuan Zhuang and Chu, {Wai Kit} and Renzhi Cai and Xianyang Zhang and Cheung, {Herman S.} and Block, {Norman L.} and Pang, {Chi Pui} and Schally, {Andrew V.} and Hao Zhang",
note = "Funding Information: We thank the Li Ka Shing Foundation for generous support. This work was supported by a block grant from the University Grants Committee Hong Kong (to C.P.P.) and in part by National Natural Science Foundation of China Grants 81071736, 30973508, and 81572876 and the Clinical Research Enhancement Initiative of Shantou University Medical College Grants 201412 and 201421 (all to H.Z.), by funding for the Collaborative and Creative Center, Molecular Diagnosis and Personalized Medicine, Shantou University, Guangdong Province (H.Z.), and by funding from the Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases. The work at the Veterans Affairs Medical Center, Miami, was supported by the Medical Research Service of the Department of Veterans Affairs (A.V.S.), the South Florida Veterans Affairs Foundation for Research and Education (A.V.S.), and the Sylvester Comprehensive Cancer Center, Miller School of Medicine of the University of Miami (A.V.S.). Publisher Copyright: {\textcopyright} 2016, National Academy of Sciences. All rights reserved.",
year = "2016",
month = dec,
day = "20",
doi = "10.1073/pnas.1618582114",
language = "English (US)",
volume = "113",
pages = "14745--14750",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "51",
}