ArticleGenetics and molecular biology
Identification of novel mutations of Insulin Receptor Substrate 1 (IRS1) in tumor samples of non-small cell lung cancer (NSCLC): Implications for aberrant insulin signaling in development of cancer.
Article in Genetics and molecular biology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- Circulating tumor DNA predicts clinical benefits of immune checkpoint blockade in HER2-negative patients with advanced gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Spatiotemporal Expression of IRS-1 During Brain Development and its Role in Neural Stem Cell Differentiation.Neuromolecular medicine · 2025Article
- Identification of cancer driver genes based on hierarchical weak consensus model.Health information science and systems · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- DriverMP enables improved identification of cancer driver genes.GigaScience · 2022Article
- The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma: New Potential Perspectives.International journal of molecular sciences · 2022Review
- Insulin Receptor Substrate 1 Is Involved in the Phycocyanin-Mediated Antineoplastic Function of Non-Small Cell Lung Cancer Cells.Molecules (Basel, Switzerland) · 2021Article
- Association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer in Turkish subjects.Oncology letters · 2020Article
- Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma.International journal of medical sciences · 2020Article
- Article
- Targeting the "PVR-TIGIT axis" with immune checkpoint therapies.F1000Research · 2020Review
- Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC).PloS one · 2019Article
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is the leading cause of cancer-related death, and NSCLC constitutes nearly 85%-90% of all cases. The IRS proteins function as adaptors and transmit signals from multiple receptors. Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. Therefore, we thought that gain of function mutantions of IRS1 could be related to development of lung cancer. In line with this, we wanted determine whether the IRS1 gene was mutated in the coding regions surrounding YXXM motifs. We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. We generated IRS1 expression vectors harboring p.S668T, p.D674H and double mutants. Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. Also, our mutants induced proliferation, glucose uptake, inhibited the migration of 293T cells and affected the responsiveness of the cells to cisplatin and radiation. Our results suggest that these novel mutations play a role in the phenotype of lung cancer.
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Registered trials
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