Hepatitis C virus(HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cau...Hepatitis C virus(HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides(PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases. PIs are implicated in a vast array of cellular responses that are central to morphogenesis, such as cytoskeletal changes, cytokinesis and the recruitment of downstream effectors to govern mechanisms involved in polarization and lumen formation. Important reviews of the literature identified phosphatidylinositol(Ptd Ins) 4-kinases, and their lipid products Ptd Ins(4)P, as critical regulators of the HCV life cycle. SH2-containing inositol polyphosphate 5-phosphatase(SHIP2), phosphoinositide 3-kinase(PI3K) and their lipid products Ptd Ins(3,4)P2 and Ptd Ins(3,4,5)P3, respectively, play an important role in the cell membrane and are key to the establishment of apicobasal polarity and lumen formation. In this review, we will focus on these new functions of PI3 K and SHIP2, and their deregulation by HCV, causing a disruption of apicobasal polarity, actin organization and extracellular matrix assembly. Finally we will highlight the involvement of this pathway in the event of insulin resistance and nonalcoholic fatty liver disease related to HCV infection.展开更多
hSHIP, a human SH2-containing inositol-5-phosphatase, acts as a negative regulator of proliferation and survival in hematopoietic cells. Therefore, hSHIP may play a crucial role in suppression of cervical cancer HeLa ...hSHIP, a human SH2-containing inositol-5-phosphatase, acts as a negative regulator of proliferation and survival in hematopoietic cells. Therefore, hSHIP may play a crucial role in suppression of cervical cancer HeLa cells. In this study, pcDNA3.1-hSHIP-GFP plas- mid was constructed and transfected into HeLa cells with Lipofectamine2000, stably transfected HeLa cells were established and their responses were investigated by Flow cytometry, MTT, tumorigenicity in nude mice, RT-PCR and ELISA assays. The results showed that the expression of hSHIP significantly induced S-phase arrest, cell growth inhibition, and down-regulation of Aktl/2 mRNA and p-Akt in HeLa cells. Our study supports an important role for hSHIP in suppression of cervical cancer HeLa cells, which may prove to be a novel therapeutic option for non-hematopoietic cancers.展开更多
基金Supported by Agence Nationale de Recherche sur le Sida et les hépatites(ANRS,France),Ligue contre le cancer,France
文摘Hepatitis C virus(HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides(PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases. PIs are implicated in a vast array of cellular responses that are central to morphogenesis, such as cytoskeletal changes, cytokinesis and the recruitment of downstream effectors to govern mechanisms involved in polarization and lumen formation. Important reviews of the literature identified phosphatidylinositol(Ptd Ins) 4-kinases, and their lipid products Ptd Ins(4)P, as critical regulators of the HCV life cycle. SH2-containing inositol polyphosphate 5-phosphatase(SHIP2), phosphoinositide 3-kinase(PI3K) and their lipid products Ptd Ins(3,4)P2 and Ptd Ins(3,4,5)P3, respectively, play an important role in the cell membrane and are key to the establishment of apicobasal polarity and lumen formation. In this review, we will focus on these new functions of PI3 K and SHIP2, and their deregulation by HCV, causing a disruption of apicobasal polarity, actin organization and extracellular matrix assembly. Finally we will highlight the involvement of this pathway in the event of insulin resistance and nonalcoholic fatty liver disease related to HCV infection.
基金supported by 985 Research Foundation of Xiamen UniversityResearch Foundation of Cancer Research Center,Xiamen University
文摘hSHIP, a human SH2-containing inositol-5-phosphatase, acts as a negative regulator of proliferation and survival in hematopoietic cells. Therefore, hSHIP may play a crucial role in suppression of cervical cancer HeLa cells. In this study, pcDNA3.1-hSHIP-GFP plas- mid was constructed and transfected into HeLa cells with Lipofectamine2000, stably transfected HeLa cells were established and their responses were investigated by Flow cytometry, MTT, tumorigenicity in nude mice, RT-PCR and ELISA assays. The results showed that the expression of hSHIP significantly induced S-phase arrest, cell growth inhibition, and down-regulation of Aktl/2 mRNA and p-Akt in HeLa cells. Our study supports an important role for hSHIP in suppression of cervical cancer HeLa cells, which may prove to be a novel therapeutic option for non-hematopoietic cancers.
