Inflammation-Driven Carcinogenesis is Mediated through STING
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ABSTRACT:
PROVIDER: PRJNA246777 | ENA |
REPOSITORIES: ENA
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Project description:Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease Total RNA obtained from DMBA or acetone treated wild type (WT) or STING deficient (SKO) mouse skin or skin tumor was examined for gene expression.
2014-05-31 | E-GEOD-57604 | biostudies-arrayexpress
Project description:Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease Total RNA obtained from wild type murine embryonic fibroblasts (WT MEFs), STING deficient MEFs (SKO), Trex1 deficient MEFs (TKO), and both STING and Trex1 deficient MEFs (STKO) treated with DMBA and examined cytokine production by these cells.
2014-05-31 | E-GEOD-57603 | biostudies-arrayexpress
Project description:Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease
2014-05-31 | GSE57604 | GEO
Project description:Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease
2014-05-31 | GSE57603 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-31 | E-GEOD-57605 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4998973 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-05-31 | GSE57605 | GEO
Project description:BRCA1 loss leads to tumor cell transcriptional reprogramming, resulting in a DNA damage-driven, mandatory cell-autonomous type I IFN inflammatory activation mediated by STING and TREX1/2. PARP inhibition augmented this immunoreactivity, creating contextual lethality to dual immune checkpoint blockade (ICB) in vivo. BRCA1-deficient tumor can escape T-cell inflammation through targeted deletion or methylation of the DNA sensing/IFN pathway genes, such as STING, IFNB1 or the chemokine CCL5. Alternatively, BRCA-mutated carcinomas retaining immunoreactivity upregulate their VEGF-A expression driven by STING, which mediates immune resistance and tumor progression. STING elimination attenuated tumor growth and abrogated therapeutic resistance to dual ICB. VEGF-A blockade synergized with immune checkpoint blockade and/or PARP inhibition to control outgrowth of Brca1-/- ovarian tumors, offering opportunities for rational combination therapy of cancers with homologous recombination repair deficiency (HRD).
2021-06-16 | GSE162935 | GEO
Project description:Inflammation-Driven Carcinogenesis is Mediated through STING [skin]
| PRJNA246781 | ENA
Project description:Inflammation-Driven Carcinogenesis is Mediated through STING [MEFs]
| PRJNA246780 | ENA