Dataset Information

PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling.

ABSTRACT: Dengue virus (DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV for virus replication in which lipid droplets (LDs) play a key role during the virus lifecycle. In this study, we reveal a novel role for phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in LDs-mediated DENV infection. We demonstrate that PTEN expression is downregulated upon DENV infection through post-transcriptional regulation and, in turn, PTEN overexpression enhances DENV replication. PTEN lipid phosphatase activity was found to decrease cellular LDs area and number through Akt/FoxO1/Maf1 signaling, which, together with autophagy, enhanced DENV replication and virus production. We therefore provide mechanistic insight into the interaction between lipid metabolism and the DENV replication cycle.

SUBMITTER: Liu B

PROVIDER: S-EPMC8257821 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling.

Liu Bin B Gao Ting-Ting TT Fu Xiao-Yu XY Xu Zhen-Hao ZH Ren Hao H Zhao Ping P Qi Zhong-Tian ZT Qin Zhao-Ling ZL

Virologica Sinica 20201012 3

Dengue virus (DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV for virus replication in which lipid droplets (LDs) play a key role during the virus lifecycle. In this study, we reveal a novel role for phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in LDs-mediated DENV infection. We demonstrate that PTEN expression is downregulat ...[more]

PMID: 33044659

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Project description:BackgroundPhosphatase and tensin homolog (PTEN) is an important tumor suppressor gene, and its encoded protein has activities of both a protein phosphatase and a lipid phosphatase. However, the substitution effect of protein phosphatase activity remains unclear. PI3K/Akt is the most common pathway negatively regulated by PTEN. The Hippo and PI3K/Akt pathways have a joint effect in regulating cell proliferation and apoptosis. Therefore, how PTEN lipid phosphatase inactivation contributes to the occurrence and development of gastric cancer and the potential role of the Hippo and PI3K/Akt pathways in PTEN lipid phosphatase inactivation mediated gastric tumorigenesis remain to be explored.MethodsImmunohistochemical staining was performed to detect the expression of p-PTEN and YAP in a gastric cancer tissue microarray. Stable cell lines expressing a wild-type or dominant-negative mutant PTEN were established. The proliferation and migration of stable cells were detected by MTT, BrdU, and colony-formation, transwell assay and high content analysis in vitro, and tumor growth differences were observed in xenograft nude mice. Changes in the expression of key molecules in the Hippo and Akt signaling pathways were detected by western blot. Nuclear-cytoplasm separation, immunofluorescence and coimmunoprecipitation analyses were conducted to explore the dysregulation of Hippo in the stable cell lines.ResultsPTEN lipid phosphatase inactivation strongly promoted the proliferation and migration of gastric cancer cells in vitro and tumor growth in vivo. A immunohistochemical analysis of gastric cancer tissues revealed a significant correlation between phosphorylated PTEN and nuclear YAP expression, and both were determined to be independent prognostic factors for gastric cancer. Mechanistically, PTEN lipid phosphatase inactivation abolished the MOB1-LATS1/2 interaction, decreased YAP phosphorylation and finally promoted YAP nuclear translocation, which enhanced the synergistic effect of YAP-TEAD, thus inducing cell proliferation and migration. Moreover, PTEN lipid phosphatase inactivation promoted the PI3K/Akt pathway, and disruption of YAP-TEAD-driven transcription decreased the activation of Akt in a dose-dependent manner.ConclusionsTaken together, our findings indicate that PTEN lipid phosphatase inactivation links the Hippo and PI3K/Akt pathways to promote gastric tumorigenesis and cancer development.

Dataset Information

PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling.

Publications

PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling.

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