Golgi phosphoprotein 3 (GOLPH3) promotes hepatocellular carcinoma cell aggressiveness by activating the NF-κB pathway.
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, in which the NF-κB pathway plays an important role and is constitutively activated. Better understanding of the molecular pathogenesis of HCC and the NF-κB pathway are needed to improve patient outcomes. Herein, we identified an unappreciated protein involved in NF-κB-induced activation, Golgi phosphoprotein 3 (GOLPH3). The mRNA and protein expression levels of GOLPH3 were frequently up-regulated in HCC and GOLPH3 expression correlated closely with clinical stage and survival in both the testing and validation cohorts. Ectopic over-expression of GOLPH3 in PLC/PRF/5 (PLC) and Huh7 HCC cells protected against cisplatin-induced apoptosis, promoted angiogenesis and proliferation and increased the aggressiveness of HCC cells in vitro and in vivo, whereas inhibition of GOLPH3 led to decreased aggressiveness. Through analysis of two published HCC patient profiles, GOLPH3 expression significantly correlated with NF-κB signalling. Furthermore, we demonstrated that GOLPH3 promoted K63-linked polyubiquitination of tumour necrosis factor receptor-associated factor 2 (TRAF2), receptor interacting protein (RIP) and NF-κB essential modulator (NEMO) and substantially sustained the activation of NF-κB in HCC cells. Taken together, our findings provided evidence that GOLPH3 is a prognostic and/or potential therapeutic biomarker for HCC patients and plays an important role in activation of the NF-κB pathway during HCC progression.
['Dai|Ting|T|', 'Zhang|Dongsheng|D|', 'Cai|Muyan|M|', 'Wang|Chanjuan|C|', 'Wu|Zhiqiang|Z|', 'Ying|Zhe|Z|', 'Wu|Jueheng|J|', 'Li|Mengfeng|M|', 'Xie|Dan|D|', 'Li|Jun|J|', 'Song|Libing|L|']
D000818:Animals D006528:Carcinoma, Hepatocellular D045744:Cell Line, Tumor D002478:Cells, Cultured D004195:Disease Models, Animal D018450:Disease Progression D005260:Female D064593:Heterografts D006801:Humans D066298:In Vitro Techniques D008113:Liver Neoplasms D008297:Male D008565:Membrane Proteins D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D008875:Middle Aged D016328:NF-kappa B D009361:Neoplasm Invasiveness D011379:Prognosis D015398:Signal Transduction D015996:Survival Rate
GOLPH3 NF-κB pathway biomarker HCC progression ubiquitination