ArticleProceedings of the National Academy of Sciences of the United States of America2019
p110γ deficiency protects against pancreatic carcinogenesis yet predisposes to diet-induced hepatotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Overexpression of PIK3CG in Cancer Cells Promotes Lung Cancer Cell Migration and Metastasis Through Enhanced MMPs Expression and Neutrophil Recruitment and Activation.Biochemical genetics · 2025Article
- Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.iScience · 2025Article
- Targeting the PI3K/AKT signaling pathway: an important molecular mechanism of herbal medicine in the treatment of MASLD/MASH.Frontiers in nutrition · 2025Review
- Prediction of immunotherapy response using mutations to cancer protein assemblies.Science advances · 2024Article
- Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.Nature structural & molecular biology · 2024Article
- An Insight into Different Experimental Models used for Hepatoprotective Studies: A Review.Current drug discovery technologies · 2024Review
- Dietary fat and lipid metabolism in the tumor microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs.Cell reports · 2023Article
- Development and safety of PI3K inhibitors in cancer.Archives of toxicology · 2023Review
- High expression of the phosphoinositide 3-kinase p11γ isoform can predict poor prognosis of non-small cell lung cancer.Histology and histopathology · 2022Article
- Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development.International journal of molecular sciences · 2022Article
- PI3K and AKT at the Interface of Signaling and Metabolism.Current topics in microbiology and immunology · 2022Article
- The therapeutic implications of immunosuppressive tumor aerobic glycolysis.Cellular & molecular immunology · 2022Review
- PI3Kγ promotes obesity-associated hepatocellular carcinoma by regulating metabolism and inflammation.JHEP reports : innovation in hepatology · 2021Article
- Structure of the phosphoinositide 3-kinase (PI3K) p110γ-p101 complex reveals molecular mechanism of GPCR activation.Science advances · 2021Article
- Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.EMBO molecular medicine · 2021Article
- Article
- Beyond the Genomic Mutation: Rethinking the Molecular Biomarkers of K-RAS Dependency in Pancreatic Cancers.International journal of molecular sciences · 2020Review
- For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors.Biomolecules · 2019Review
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor survival and resistance to conventional therapies. PI3K signaling is implicated in both disease initiation and progression, and specific inhibitors of selected PI3K p110 isoforms for managing solid tumors are emerging. We demonstrate that increased activation of PI3K signals cooperates with oncogenic Kras to promote aggressive PDAC in vivo. The p110γ isoform is overexpressed in tumor tissue and promotes carcinogenesis via canonical AKT signaling. Its selective blockade sensitizes tumor cells to gemcitabine in vitro, and genetic ablation of p110γ protects against Kras-induced tumorigenesis. Diet/obesity was identified as a crucial means of p110 subunit up-regulation, and in the setting of a high-fat diet, p110γ ablation failed to protect against tumor development, showing increased activation of pAKT and hepatic damage. These observations suggest that a careful and judicious approach should be considered when targeting p110γ for therapy, particularly in obese patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.