ArticlePloS one2014
Hyperglycemia promotes K-Ras-induced lung tumorigenesis through BASCs amplification.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Effect of hypoglycemic agents on survival outcomes of lung cancer patients with diabetes mellitus: A meta-analysis.Medicine · 2018 · on this mapPooled it
- Targeting the molecular crosstalk between diabetes and lung cancer for therapeutic intervention.Discover oncology · 2025Review
- Oncogenic Mutations and the Tumor Microenvironment: Drivers of Non-Small Cell Lung Cancer Progression.Cancers · 2025Review
- FFAR4 activation inhibits lung adenocarcinoma via blocking respiratory chain complex assembly associated mitochondrial metabolism.Cellular & molecular biology letters · 2024Article
- Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model.International journal of molecular sciences · 2021Article
- Towards the Development of a Female Animal Model of T1DM Using Hyaluronic Acid Nanocoated Cell Transplantation: Refinements and Considerations for Future Protocols.Pharmaceutics · 2021Article
- Defining a metabolic landscape of tumours: genome meets metabolism.British journal of cancer · 2020Review
- Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes.International journal of molecular sciences · 2019Review
- Genome-wide Analysis Reveals DNA Methylation Alterations in Obesity Associated with High Risk of Colorectal Cancer.Scientific reports · 2019Article
- Fasting Blood Glucose Level in Locally Advanced Non-Small Cell Lung Cancer: a New Prognostic Factor?Hormones & cancer · 2018Article
- Progress in the application and mechanism of metformin in treating non-small cell lung cancer.Oncology letters · 2017Article
- Review
- Comparative proteomics of a model MCF10A-KRasG12V cell line reveals a distinct molecular signature of the KRasG12V cell surface.Oncotarget · 2016Article
- Current perspectives between metabolic syndrome and cancer.Oncotarget · 2016Review
- The Apoptotic Effect of HIF-1α Inhibition Combined with Glucose plus Insulin Treatment on Gastric Cancer under Hypoxic Conditions.PloS one · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic K-Ras represents the most common molecular change in human lung adenocarcinomas, the major histologic subtype of non-small cell lung cancer (NSCLC). The presence of K-Ras mutation is associated with a poor prognosis, but no effective treatment strategies are available for K-Ras -mutant NSCLC. Epidemiological studies report higher lung cancer mortality rates in patients with type 2 diabetes. Here, we use a mouse model of K-Ras-mediated lung cancer on a background of chronic hyperglycemia to determine whether elevated circulating glycemic levels could influence oncogenic K-Ras-mediated tumor development. Inducible oncogenic K-Ras mouse model was treated with subtoxic doses of streptozotocin (STZ) to induce chronic hyperglycemia. We observed increased tumor mass and higher grade of malignancy in STZ treated diabetic mice analyzed at 4, 12 and 24 weeks, suggesting that oncogenic K-Ras increased lung tumorigenesis in hyperglycemic condition. This promoting effect is achieved by expansion of tumor-initiating lung bronchio-alveolar stem cells (BASCs) in bronchio-alveolar duct junction, indicating a role of hyperglycemia in the activity of K-Ras-transformed putative lung stem cells. Notably, after oncogene K-Ras activation, BASCs show upregulation of the glucose transporter (Glut1/Slc2a1), considered as an important player of the active control of tumor cell metabolism by oncogenic K-Ras. Our novel findings suggest that anti-hyperglycemic drugs, such as metformin, may act as therapeutic agent to restrict lung neoplasia promotion and progression.
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