Evidence map›Paper›PMID 30807634›Full record

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.

Gokhan Gorgisen, Fatma Zehra Hapil, Ozlem Yilmaz, Zafer Cetin, Suray Pehlivanoglu, Irem Hicran Ozbudak, Abdullah Erdogan, Osman Nidai Ozes

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 30 citations in OpenAlex.

  1. 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 · 2025
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  4. Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 6 institutions in 2 countries.

Gokhan GorgisenFaculty of Medicine, Van Yuzuncu Yil University, Turkey.
Fatma Zehra HapilIzmir Biotechnology and Genome Center, Izmir, Turkey.
Ozlem YilmazFaculty of Medicine, Akdeniz University, Antalya, Turkey.
Zafer CetinFaculty of Medicine, Sanko University, Gaziantep, Turkey.
Suray PehlivanogluFaculty of Science, Necmettin Erbakan University, Konya, Turkey.
Irem Hicran OzbudakFaculty of Medicine, Akdeniz University, Antalya, Turkey.
Abdullah ErdoganFaculty of Medicine, Akdeniz University, Antalya, Turkey.
Osman Nidai OzesALTAY Biopharma, San Bruno, CA, USA.
Akdeniz University · TRAltaiskiy State Nature Biosphere Reserve · RUIzmir Institute of Technology · TRNecmettin Erbakan University · TRSanko University · TRVan Yüzüncü Yıl Üniversitesi · TR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Identifiers

PMID30807634
PMCPMC6428125
OpenAlexW2917170846

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Registered trials

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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 OpenQuestion graph.