Glucose-regulated protein 94 mediates cancer progression via AKT and eNOS in hepatocellular carcinoma.

Abstract	Hepatocellular carcinoma (HCC) is a crucial health issue worldwide. High glucose-regulated protein 94 (GRP94) expression has been observed in different types of cancer, suggesting a link between tumor progression and GRP94 expression. However, the mechanisms underlying the role of GRP94 in HCC progression remain unclear. We used specific small hairpin RNA (shRNA) to manipulate GRP94 expression in HCC cells. Tissue arrays, MTT assays, xCELLigence assays, and in vivo xenograft model were performed to identify clinicopathological correlations and to analyze cell growth. We found that high GRP94 expression reflected a poor response and a lower survival rate. In vitro and in vivo studies showed that silencing GRP94 suppressed cancer progression. Mechanistically, GRP94 knockdown reduced AKT, phospho-AKT, and eNOS levels but did not influence the AMPK pathway. Our results demonstrated that GRP94 is a key molecule in HCC progression that modulates the AKT pathway and eNOS levels. Our findings suggest that GRP94 may be a new prognostic and therapeutic target for HCC.
Authors	Chien-Yu Huang, Uyanga Batzorig, Wan-Li Cheng, Ming-Te Huang, Wei- Yu Chen, Po-Li Wei, Yu-Jia Chang
Journal	Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 4 Pg. 4295-304 (Apr 2016) ISSN: 1423-0380 [Electronic] Netherlands
PMID	26493996 (Publication Type: Journal Article)
Chemical References	Membrane Glycoproteins endoplasmin NOS3 protein, human Nitric Oxide Synthase Type III Proto-Oncogene Proteins c-akt AMP-Activated Protein Kinases
Topics	AMP-Activated Protein Kinases (biosynthesis, genetics) Animals Carcinogenesis (genetics) Carcinoma, Hepatocellular (genetics, pathology) Cell Line, Tumor Cell Proliferation (genetics) Disease Progression Gene Expression Regulation, Neoplastic Humans Liver Neoplasms (genetics, pathology) Membrane Glycoproteins (antagonists & inhibitors, genetics) Mice Nitric Oxide Synthase Type III (biosynthesis, genetics) Proto-Oncogene Proteins c-akt (biosynthesis, genetics) Xenograft Model Antitumor Assays

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