Golgi protein 73, hepatocellular carcinoma and other types of cancers

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a low survival rate. The identification of mechanisms underlying the development of HCC helps uncover cellular and molecular targets for the diagnosis, prevention, and treatment of HCC. Golgi protein 73 (GP73) level is upregulated in HCC patients and potentially can be a therapeutic target. Despite many studies devoted to GP73 as a marker for HCC early diagnosis, there is little discussion about the function of GP73 in HCC tumorigenesis. Given the poor response to currently available HCC therapies, a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC. The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis. Its roles in other types of cancer are also discussed.

Keywords: Alpha-fetoprotein (AFP); Diagnostic markers; Gamma-glutamyl transferase (GGT); Golgi protein 73 (GP73); Hepatitis B virus (HBV); Hepatitis C virus (HCV); Hepatocellular carcinoma (HCC); Liver cancer.

Fig. 1.. Schematic diagrams of GP73.

GP73 has 5 domains including a short N-terminal cytoplasmic tail, transmembrane domain, coiled-coil structure, loose structure, and highly conservative domain. Abbreviation: GP73, Golgi protein 73.

Fig. 2.. Schematic illustration of the mechanisms by which GP73 expression is regulated.

GP73 is regulated by HBsAg, cytokines, hyper-activated mTORC1, HIF-2α, and miRNA. GP73 promotes the occurrence and development of HCC through inhibition of apoptosis and autophagy, as well as promoting EMT. This figure was generated using tools available in the BioRender.com. Abbreviations: DEPTOR, DEP-domain containing mTOR-interacting protein; EMT, epithelial-mesenchymal transition; GP73, Golgi protein 73; HBV, hepatitis B virus; HIF-2α, hypoxia inducible factors-2alpha; IFN-γ, interferon-gamma; IL, interleukin; mLST8, mammalian lethal with SEC13 protein 8; mTOR, mechanistic target of rapamycin; mTORC1, mechanistic target of rapamycin complex 1; PRAS40, prolin-rich Akt substrate of 40 kD; RAPTOR, regulatory-associated protein of mammalian target of rapamycin; STAT3, signal transducer and activator of transcription 3; TNF-α, tumor necrosis factor-alpha.