Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA176342 | ENA |
REPOSITORIES: ENA
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Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, M-NM-14M-NM-21 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis. Bone marrow derived macrophages from five wild type and five Rac2 -/- mutant C57BL mice.
2012-10-02 | E-GEOD-41236 | biostudies-arrayexpress
Project description:A macrophage autonomous α4β1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis
| PRJNA178015 | ENA
Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, α4β1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis. SmoA1 Tg MB tumor cells were sorted into CD15+ and CD15- populations. RNA from these samples were hybridized to Affymetrix Mouse Genome 1.0 ST array.
2012-11-15 | E-GEOD-41717 | biostudies-arrayexpress
Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, α4β1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis.
2012-11-15 | GSE41717 | GEO
Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, α4β1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis.
2012-10-02 | GSE41236 | GEO
Project description:Macrophage Syk-PI3Kγ-HIF axis controls tumor immune suppression
| PRJNA473813 | ENA
Project description:We recently identified the nonreceptor tyrosine kinase syk as a tumor suppressor in pancreatic ductal adenocarcinoma cells. Reintroduction of syk into Panc1 cells promoted a more differentiated phenotype and retarded invasion and tumorigenic growth. Gene array analysis identified over 2,000 transcripts differentially expressed at FDR<0.01. Among these were members of the MMP2 axis, which were subsequently shown to regulate Panc1 invasion. Experiment Overall Design: Affymetrix global gene arrays were used to analyse differences in gene expression patterns in Panc1 cells stably reexpressing syk, or vector-only mock controls. RNA was harvested from cells grown under identical conditions in standard culture.
2009-09-18 | E-GEOD-18000 | biostudies-arrayexpress
Project description:Macrophages (MΘs) play a critical role in tumor growth, immunosuppression and inhibition of adaptive immune responses in cancer. Hence, targeting signaling pathways in MΘs that promote tumor immunosuppression will provide therapeutic benefit. PI3Kγ has been recently established by our group and others as a novel immuno-oncology target. Herein, we report that macrophage Syk drives polarization of immunosuppressive macrophages which establish an immunosuppressive tumor microenvironment in in vivo syngeneic tumor models. Genetic or pharmacological blockade of Syk in MΘs promotes a pro-inflammatory MΘ phenotype, restores CD8+ T cell activity, destabilizes HIF under hypoxia, and stimulates antitumor immune response. Moreover, we have developed in silico the “first in class” dual Syk/PI3K inhibitor, SRX3207, for the combinatorial inhibition of Syk and PI3K in one small molecule to activate anti-tumor immunity in vivo. This chemotype shows great efficacy in various tumor models and represents a new therapeutic approach to treat devastating cancers. Significance: Our data indicate a central role of Syk in macrophage transcriptional programming leading to inhibition of adaptive immune responses. Furthermore, SRX3207 blocks macrophage expression of immunosuppressive factors and activates anti-tumor immune responses, validating the concept of combined Syk and PI3K inhibition as an effective approach to treat macrophage driven cancers.
2020-09-01 | GSE115109 | GEO
Project description:Glioblastoma multiforme (GBM), the most lethal type of primary brain tumor, exhibits profound metabolic plasticity driven by glioma stem cells (GSCs), which sustain therapeutic resistance and tumor recurrence. Here, we elucidate a novel epigenetic-metabolic axis mediated by the histone acetyltransferase KAT7 that orchestrates oxidative phosphorylation (OXPHOS) dominance in GSCs. Through a multiomics analysis, we demonstrated that KAT7 is preferentially upregulated in GBM, particularly in the classical subtype and in GSC-enriched populations, where it activates RAC2 expression via H3K14 acetylation of its promoter. Mechanistically, KAT7-mediated RAC2 upregulation triggers PAK1/2/3 phosphorylation, increasing tricarboxylic acid cycle (TCA) and ATP production. Genetic ablation of KAT7 impairs GSC self-renewal, induces apoptosis, and suppresses tumor growth in orthotopic xenograft models. Conversely, KAT7 overexpression or pharmacological activation of the KAT7–RAC2 axis restores metabolic fitness and malignant phenotypes. Notably, the small-molecule inhibitor WM-3835, which targets KAT7, exhibits potent anti-GBM efficacy by disrupting H3K14ac and mitochondrial respiration, leading to prolonged survival in mice. Our study identifies KAT7 as a master regulator of GSC metabolism, revealing an actionable therapeutic target in GBM progression. Targeting the KAT7–RAC2–PAK axis may represent a precise strategy to overcome metabolic plasticity-driven therapeutic resistance in this recalcitrant malignancy.
2026-09-16 | GSE328308 | GEO
Project description:Glioblastoma multiforme (GBM), the most lethal type of primary brain tumor, exhibits profound metabolic plasticity driven by glioma stem cells (GSCs), which sustain therapeutic resistance and tumor recurrence. Here, we elucidate a novel epigenetic-metabolic axis mediated by the histone acetyltransferase KAT7 that orchestrates oxidative phosphorylation (OXPHOS) dominance in GSCs. Through a multiomics analysis, we demonstrated that KAT7 is preferentially upregulated in GBM, particularly in the classical subtype and in GSC-enriched populations, where it activates RAC2 expression via H3K14 acetylation of its promoter. Mechanistically, KAT7-mediated RAC2 upregulation triggers PAK1/2/3 phosphorylation, increasing tricarboxylic acid cycle (TCA) and ATP production. Genetic ablation of KAT7 impairs GSC self-renewal, induces apoptosis, and suppresses tumor growth in orthotopic xenograft models. Conversely, KAT7 overexpression or pharmacological activation of the KAT7–RAC2 axis restores metabolic fitness and malignant phenotypes. Notably, the small-molecule inhibitor WM-3835, which targets KAT7, exhibits potent anti-GBM efficacy by disrupting H3K14ac and mitochondrial respiration, leading to prolonged survival in mice. Our study identifies KAT7 as a master regulator of GSC metabolism, revealing an actionable therapeutic target in GBM progression. Targeting the KAT7–RAC2–PAK axis may represent a precise strategy to overcome metabolic plasticity-driven therapeutic resistance in this recalcitrant malignancy.
2026-09-16 | GSE328130 | GEO