國家衛生研究院 NHRI:Item 3990099045/10287

NHRI > Institute of Molecular and Genomic Medicine > Shiu-Feng Kathy Huang > Periodical Articles > Item 3990099045/10287

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10287

Title:	Characterization of the GNMT-HectH9-PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma
Authors:	Li, CH;Yen, CH;Chen, YF;Lee, KJ;Fang, CC;Zhang, X;Lai, CC;Huang, SF;Lin, HK;Arthur Chen, YM
Contributors:	Institute of Molecular and Genomic Medicine
Abstract:	The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N-methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9-mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation. An elevated PREX2 protein expression accompanied by activation of AKT was observed in the liver of Gnmt knockout mice. PREX2 protein expression was upregulated in 54.9% of human HCC samples, while its mRNA level was comparable in tumor and tumor-adjacent tissue, suggesting a post-translational alteration of PREX2 expression. Higher level of PREX2 in the tumor tissues was associated with poorer survival. These results reveal a novel mechanism in which GNMT participates in AKT signaling and HCC tumorigenesis by promoting HectH9-mediated PREX2 degradation. This article is protected by copyright. All rights reserved.
Date:	2017-05
Relation:	International Journal of Cancer. 2017 May;140(10):2284-2297.
Link to:	http://dx.doi.org/10.1002/ijc.30652
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0020-7136&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000399313200012
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85016093669
Appears in Collections:	[Shiu-Feng Kathy Huang] Periodical Articles

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