Hepatitis B Virus X Protein Confers Resistance of Hepatoma Cells to Anoikis by Up-regulating and Activating p21-Activated Kinase 1

Xu, Jiejie; Liu, Haiou; Chen, Lin; Wang, Shanshan; Zhou, Lei; Yun, Xiaojing; Sun, Linlin; Wen, Yumei; Gu, Jianxin

doi:10.1053/j.gastro.2012.03.053

Cited by 74 publications

(77 citation statements)

References 35 publications

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“…27,28 The Akt family members of serine/threonine kinases including Akt1 and Akt2 have been found to diametrically orchestrate diverse macrophage polarization via miR-155-mediated C/EBPb signal regulation. 29,30 Although our previous findings indicated the crucial role of PAK1 in anoikis resistance and hepatoma progression, 31 the potential significance of PAKs family in macrophage polarization remains far from fully understood.…”

mentioning

confidence: 94%

Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway

Zhang

Liu

et al. 2014

Cell Death Differ

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Serine/threonine kinase family members p21-activated kinases (PAKs) are important regulators of cytoskeletal remodeling and cell motility in mononuclear phagocytic system, but their role in macrophage differentiation and polarization remains obscure. We have shown here that inflammatory stimuli induced PAK1 overexpression in human and murine macrophages. Elevated expression of PAK1 contributed to macrophage M1 polarization and lipopolysaccharide (LPS)-induced endotoxin shock. We further observed that epigenetic loss of microRNA let-7c due to enhancer of zeste homolog 2 (EZH2) upregulation determined PAK1 elevation and inflammatory phenotype in M1 macrophages. EZH2/let-7c/PAK1 axis promotes macrophage M1 polarization via NIK-IKK-NF-jB signaling. Moreover, pharmacological and genetic ablation with EZH2/let-7c/PAK1 axis blunted inflammatory phenotype in M1 macrophages. Critically, either myeloid-restricted PAK1 deletion (PAK1 Lyz2cre ) or pharmacological and genetic ablation with EZH2/let-7c/PAK1 signal resulted in resistance to LPS-induced endotoxin shock via blunting macrophage M1 polarization. PAK1, therefore, is an essential controller of inflammatory macrophage polarization, regulating immune responses against pathogenic stimuli.

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mentioning

confidence: 94%

Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway

Zhang

Liu

et al. 2014

Cell Death Differ

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“…Western Blotting and Co-immunoprecipitation-Protein extraction from cultured cells or tissues, Western blot analysis, and co-immunoprecipitation were carried out as previously described (54,55). Antibodies used here were obtained from Santa Cruz and included those against ␤-actin, GAPDH, DAI, FLAG, HA, and IgG-HRP.…”

Section: Methodsmentioning

confidence: 99%

“…Luciferase Reporter Assay-Luciferase activity were performed as described previously (55). In brief, HEK293 cells were cotransfected with the mixture of 0.1 g of NF-B luciferase reporter plasmid (pNF-B-Luc; Stratagene, La Jolla, CA) or 0.1 g of IRF3 luciferase reporter plasmid (pIRF3-Luc), 0.1 g of pRL-SV40 containing Renilla luciferase gene (pRL-SV40-Renilla-Luc; Promega, Madison, WI), with or without the indicated amounts of pcDNA3-DAI (pDAI) or pcDNA3 vector using Lipofectamine 2000 (Invitrogen) following the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Total amounts of plasmid DNA were equalized with empty control vector. After 36 h, cells were left untreated or treated with the indicated amounts of UnALD-DNA or ALD-DNA for another 12 h. Luciferase activities were determined using the Luciferase Reporter Assay System according to the manufacturer's instructions (Promega, Madison, WI) (55). Luciferase activities were calculated as the percentage of the empty pcDNA3 vector and the values were normalized to the activity of Renilla luciferase.…”

Section: Methodsmentioning

confidence: 99%

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DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

Zhang

Zhou

et al. 2013

Journal of Biological Chemistry

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Background: Macrophage M2b polarization conferred by self-DNA immunization initiates and propagates lupus nephritis. Results: Knockdown of DNA-dependent activator of interferon-regulatory factors (DAI) ameliorates SLE syndrome via blunting macrophage M2b polarization. Conclusion: DAI functions as a DNA sensor in self-DNA-induced macrophage M2b polarization and lupus nephritis. Significance: We disclose the mechanism by which self-DNA induces macrophage M2b polarization and lupus nephritis.

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“…Xu et al (70) suggested that HBx may upregulate serine/threonine p21-activated kinase 1, which is involved in the regulation of cytoskeletal dynamics and the protection of cells from anoikis, in order to promote the growth of tumors in mice. HBx also promotes cell proliferation via the upregulation of LASP-1, and inhibits the expression of LASP-1 to decrease the accumulation of HBx bearing cells at the G2/M phase of the cell cycle (23).…”

Section: The Cellular Cytoskeletal Proteins Associated With Cellular mentioning

confidence: 99%

The regulation of proteins associated with the cytoskeleton by hepatitis B virus X protein during hepatocarcinogenesis

et al. 2017

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Abstract. Hepatocellular carcinoma (HCC) is a major malignant disease worldwide, and chronic hepatitis B virus (HBV) infection is one of the primary causes for this type of cancer. Hepatitis B virus X protein (HBx) is a non-structural protein encoded by the viral genome that has significant effects on the pathogenesis of HCC. With the development of high-throughput assays and technologies, the abnormal HBx-induced expression of certain cellular proteins with assorted biological functions has been investigated. These target proteins identified by various methods include specific proteins associated with the cellular cytoskeleton, which contribute to HBx-induced hepatocarcinogenesis. In addition, the cytoskeletal proteins deregulated by HBx are involved in cell morphogenesis, adhesion, migration and proliferation. This review aims to summarize the current understanding of the expression profiles of HBx-associated cytoskeletal proteins, as well as their complex functions and underlying mechanisms in hepatocarcinogenesis. Considering that the potential therapeutics for various types of tumors may function through the stabilization of cytoskeletal proteins in order to restrict cellular movement and limit intracellular processes, clarifying the mechanisms underlying protein-associated cytoskeleton dysregulation by HBx may provide novel possibilities and potent therapeutic targets for HBV-associated HCC. Contents

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Hepatitis B Virus X Protein Confers Resistance of Hepatoma Cells to Anoikis by Up-regulating and Activating p21-Activated Kinase 1

Cited by 74 publications

References 35 publications

Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway

Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway

DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

The regulation of proteins associated with the cytoskeleton by hepatitis B virus X protein during hepatocarcinogenesis

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