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Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization
by
Li, Cong
, Liu, Yanchun
, Zhang, Ting
, Gu, Feng
, Zhang, Hongan
in
692/4028
/ 692/4028/67
/ Animals
/ Bone marrow
/ c-Mer Tyrosine Kinase - metabolism
/ Cancer
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - immunology
/ Carcinoma, Hepatocellular - metabolism
/ Carcinoma, Hepatocellular - pathology
/ Cell Line, Tumor
/ Cell Movement
/ Cell Proliferation
/ Cells
/ Cholecystokinin
/ Cyclic AMP-Dependent Protein Kinases - metabolism
/ Cytokines
/ Ethanol
/ Flow cytometry
/ Gene expression
/ Gpr109A
/ Hepatocellular carcinoma
/ Humanities and Social Sciences
/ Humans
/ Immune microenvironment
/ Immunohistochemistry
/ Invasiveness
/ Leukocyte migration
/ Liver cancer
/ Liver Neoplasms - genetics
/ Liver Neoplasms - immunology
/ Liver Neoplasms - metabolism
/ Liver Neoplasms - pathology
/ Macrophages
/ Macrophages - metabolism
/ MerTK
/ Mice
/ Mice, Knockout
/ Microenvironments
/ multidisciplinary
/ Phagocytosis
/ Phenotypes
/ Phosphorylation
/ Polarization
/ Proteases
/ Proteins
/ Receptors, G-Protein-Coupled - genetics
/ Receptors, G-Protein-Coupled - metabolism
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Transforming Growth Factor beta - metabolism
/ Tumor Microenvironment
/ Tumor necrosis factor-TNF
/ Western blotting
2025
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Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization
by
Li, Cong
, Liu, Yanchun
, Zhang, Ting
, Gu, Feng
, Zhang, Hongan
in
692/4028
/ 692/4028/67
/ Animals
/ Bone marrow
/ c-Mer Tyrosine Kinase - metabolism
/ Cancer
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - immunology
/ Carcinoma, Hepatocellular - metabolism
/ Carcinoma, Hepatocellular - pathology
/ Cell Line, Tumor
/ Cell Movement
/ Cell Proliferation
/ Cells
/ Cholecystokinin
/ Cyclic AMP-Dependent Protein Kinases - metabolism
/ Cytokines
/ Ethanol
/ Flow cytometry
/ Gene expression
/ Gpr109A
/ Hepatocellular carcinoma
/ Humanities and Social Sciences
/ Humans
/ Immune microenvironment
/ Immunohistochemistry
/ Invasiveness
/ Leukocyte migration
/ Liver cancer
/ Liver Neoplasms - genetics
/ Liver Neoplasms - immunology
/ Liver Neoplasms - metabolism
/ Liver Neoplasms - pathology
/ Macrophages
/ Macrophages - metabolism
/ MerTK
/ Mice
/ Mice, Knockout
/ Microenvironments
/ multidisciplinary
/ Phagocytosis
/ Phenotypes
/ Phosphorylation
/ Polarization
/ Proteases
/ Proteins
/ Receptors, G-Protein-Coupled - genetics
/ Receptors, G-Protein-Coupled - metabolism
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Transforming Growth Factor beta - metabolism
/ Tumor Microenvironment
/ Tumor necrosis factor-TNF
/ Western blotting
2025
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Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization
by
Li, Cong
, Liu, Yanchun
, Zhang, Ting
, Gu, Feng
, Zhang, Hongan
in
692/4028
/ 692/4028/67
/ Animals
/ Bone marrow
/ c-Mer Tyrosine Kinase - metabolism
/ Cancer
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - immunology
/ Carcinoma, Hepatocellular - metabolism
/ Carcinoma, Hepatocellular - pathology
/ Cell Line, Tumor
/ Cell Movement
/ Cell Proliferation
/ Cells
/ Cholecystokinin
/ Cyclic AMP-Dependent Protein Kinases - metabolism
/ Cytokines
/ Ethanol
/ Flow cytometry
/ Gene expression
/ Gpr109A
/ Hepatocellular carcinoma
/ Humanities and Social Sciences
/ Humans
/ Immune microenvironment
/ Immunohistochemistry
/ Invasiveness
/ Leukocyte migration
/ Liver cancer
/ Liver Neoplasms - genetics
/ Liver Neoplasms - immunology
/ Liver Neoplasms - metabolism
/ Liver Neoplasms - pathology
/ Macrophages
/ Macrophages - metabolism
/ MerTK
/ Mice
/ Mice, Knockout
/ Microenvironments
/ multidisciplinary
/ Phagocytosis
/ Phenotypes
/ Phosphorylation
/ Polarization
/ Proteases
/ Proteins
/ Receptors, G-Protein-Coupled - genetics
/ Receptors, G-Protein-Coupled - metabolism
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
/ Transforming Growth Factor beta - metabolism
/ Tumor Microenvironment
/ Tumor necrosis factor-TNF
/ Western blotting
2025
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Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization
Journal Article
Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization
2025
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Overview
To delineate Gpr109A’s role and mechanisms in modulating the immune microenvironment of hepatocellular carcinoma. Employing Gpr109A-knockout mice and in vitro co-cultures of hepatocellular carcinoma cells with macrophages, this study utilized a suite of techniques, including lentiviral vectors for stable cell line establishment, Western blotting, cell scratch, CCK-8, transwell assays, flow cytometry, immunohistochemistry and phagocytosis assay to assess various cellular behaviors and interactions. Gpr109A deletion markedly reduced the oncogenic potential of H22 cells, both in vivo and when co-cultured with knockout macrophages, impairing their growth, invasion, and migration. In Gpr109A-knockout macrophages, an upregulation of MerTK and a reduction in immunosuppressive cytokine release were observed, indicating a shift towards an M2c macrophage phenotype. This shift is linked to Gpr109A’s role in promoting protease overexpression and inhibiting SHP2 phosphorylation, crucial for enhancing cancer cell proliferation and invasiveness. Gpr109A significantly influences macrophage polarization to the M2c type, augmenting hepatocellular carcinoma cell aggressiveness.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ c-Mer Tyrosine Kinase - metabolism
/ Cancer
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - immunology
/ Carcinoma, Hepatocellular - metabolism
/ Carcinoma, Hepatocellular - pathology
/ Cells
/ Cyclic AMP-Dependent Protein Kinases - metabolism
/ Ethanol
/ Gpr109A
/ Humanities and Social Sciences
/ Humans
/ Liver Neoplasms - immunology
/ Liver Neoplasms - metabolism
/ MerTK
/ Mice
/ Proteins
/ Receptors, G-Protein-Coupled - genetics
/ Receptors, G-Protein-Coupled - metabolism
/ Science
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