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

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dc.contributor.authorGorgisen, Gokhan
dc.contributor.authorHapil, Fatma Zehra
dc.contributor.authorYilmaz, Ozlem
dc.contributor.authorCetin, Zafer
dc.contributor.authorPehlivanoglu, Suray
dc.contributor.authorOzbudak, Irem Hicran
dc.contributor.authorErdogan, Abdullah
dc.date.accessioned2024-02-23T14:30:08Z
dc.date.available2024-02-23T14:30:08Z
dc.date.issued2019
dc.departmentNEÜen_US
dc.description.abstractLung 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.en_US
dc.identifier.doi10.1590/1678-4685-GMB-2017-0307
dc.identifier.endpage25en_US
dc.identifier.issn1415-4757
dc.identifier.issn1678-4685
dc.identifier.issue1en_US
dc.identifier.pmid30807634en_US
dc.identifier.scopus2-s2.0-85067306659en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage15en_US
dc.identifier.urihttps://doi.org/10.1590/1678-4685-GMB-2017-0307
dc.identifier.urihttps://hdl.handle.net/20.500.12452/15030
dc.identifier.volume42en_US
dc.identifier.wosWOS:000461467100003en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSoc Brasil Geneticaen_US
dc.relation.ispartofGenetics And Molecular Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectIrs1en_US
dc.subjectNsclcen_US
dc.subjectInsulin Signalingen_US
dc.subjectLung Canceren_US
dc.subjectIrs Proteinsen_US
dc.titleIdentification 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 canceren_US
dc.typeArticleen_US

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