Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma  

作　　者：Yiming Liu Xinyang Hu Sining Zhou Ting Sun Feiyan Shen Linghui Zeng 

机构地区：[1]Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province,Hangzhou City University School of Medicine,Hangzhou 310015,China [2]Laboratory of Cancer Biology,Key Laboratory of Biotherapy of Zhejiang Province,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310017,China [3]Cancer Center,Zhejiang University,Hangzhou 310058,China [4]Life Sciences Institute,Zhejiang University,Hangzhou 310058,China [5]Department of Pathology,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China

出　　处：《Research》2025年第1期739-751,共13页研究(英文)

基　　金：supported by the National Natural Science Foundation of China under grant 82103397 to Y.L.;R&D Program of Zhejiang Province under grant 2024C03142 to L.Z.

摘　　要：Golgi protein 73(GP73),a resident protein of the Golgi apparatus,is notably elevated in hepatocellular carcinoma(HCC).While its critical role in remodeling the tumor microenvironment(TME)is recognized,the intricate mechanisms are not fully understood.This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2(PHD-2)in a competitive manner,thereby impeding the hydroxylation of hypoxia-induced factor-1α(HIF-1α).The effect above promotes the production and secretion of vascular endothelial growth factor A(VEGFA).Moreover,exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells(HUVECs)and competitively interact with HECTD1,an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2(GRB2).This interaction stabilizes GRB2,thereby activating the Ras-mitogen-activated protein kinase(MAPK)signaling pathway.Consequently,escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells,fostering angiogenesis in the TME.Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.

关 键 词：golgi apparatusis remodeling tumor microenvironment tme ANGIOGENESIS hepatocellular carcinoma prolyl hydroxylase golgi protein 

分 类 号：R735.7[医药卫生—肿瘤]