ArticleCancer research2015
PIK3CA(H1047R) Accelerates and Enhances KRAS(G12D)-Driven Lung Tumorigenesis.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
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- Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).International journal of molecular medicine · 2026Review
- Systemic immunometabolic profiling classifies cisplatin sensitivity states using interpretable machine learning.iScience · 2026Article
- Concurrent PIK3CA mutant promotes cachexia through inflammatory signaling in EGFR mutant lung cancer.Nature communications · 2025Article
- Pathogenesis and current status of the treatment of lung cancer associated with idiopathic pulmonary fibrosis.Respiratory research · 2025Review
- Oncogenic context shapes the fitness landscape of tumor suppression.Nature communications · 2023Article
- Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression.International journal of molecular sciences · 2023Article
- Chronic obstructive pulmonary disease alters the genetic landscape and tumor immune microenvironment in lung cancer patients.Frontiers in oncology · 2023Article
- Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis.Acta pharmaceutica Sinica. B · 2022Review
- The origins and genetic interactions of KRAS mutations are allele- and tissue-specific.Nature communications · 2021Article
- Review
- Progress towards non-small-cell lung cancer models that represent clinical evolutionary trajectories.Open biology · 2021Review
- Development of a miniaturized 3D organoid culture platform for ultra-high-throughput screening.Journal of molecular cell biology · 2020Article
- Mutationally-activated PI3'-kinase-α promotes de-differentiation of lung tumors initiated by the BRAFeLife · 2019Article
- OncogenicProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mouse Models for Exploring the Biological Consequences and Clinical Significance ofBiomolecules · 2019Review
- In silico identification of key genes and signaling pathways targeted by a panel of signature microRNAs in prostate cancer.Medical oncology (Northwood, London, England) · 2019Article
- Activating Mutations inClinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Simultaneous inhibition of PI3Kα and CDK4/6 synergistically suppresses KRAS-mutated non-small cell lung cancer.Cancer biology & medicine · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
KRAS-activating mutations drive human non-small cell lung cancer and initiate lung tumorigenesis in genetically engineered mouse (GEM) models. However, in a GEM model of KRAS(G12D)-induced lung cancer, tumors arise stochastically following a latency period, suggesting that additional events are required to promote early-stage tumorigenic expansion of KRAS(G12D)-mutated cells. PI3Kα (PIK3CA) is a direct effector of KRAS, but additional activation of PI3'-lipid signaling may be required to potentiate KRAS-driven lung tumorigenesis. Using GEM models, we tested whether PI3'-lipid signaling was limiting for the promotion of KRAS(G12D)-driven lung tumors by inducing the expression of KRAS(G12D) in the absence and presence of the activating PIK3CA(H1047R) mutation. PIK3CA(H1047R) expression alone failed to promote tumor formation, but dramatically enhanced tumorigenesis initiated by KRAS(G12D). We further observed that oncogenic cooperation between KRAS(G12D) and PIK3CA(H1047R) was accompanied by PI3Kα-mediated regulation of c-MYC, GSK3β, p27(KIP1), survivin, and components of the RB pathway, resulting in accelerated cell division of human or mouse lung cancer-derived cell lines. These data suggest that, although KRAS(G12D) may activate PI3Kα by direct biochemical mechanisms, PI3'-lipid signaling remains rate-limiting for the cell-cycle progression and expansion of early-stage KRAS(G12D)-initiated lung cells. Therefore, we provide a potential mechanistic rationale for the selection of KRAS and PIK3CA coactivating mutations in a number of human malignancies, with implications for the clinical deployment of PI3' kinase-targeted therapies.
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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 Socratic graph.