ArticleScientific reports2013
IGF-1R/epithelial-to-mesenchymal transition (EMT) crosstalk suppresses the erlotinib-sensitizing effect of EGFR exon 19 deletion mutations.
Article in Scientific reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 94 citations in OpenAlex.
- Epithelial-mesenchymal transition (EMT) and its role in acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) chemoresistance in non-small cell lung cancer (NSCLC).Cancer pathogenesis and therapy · 2025Review
- Drug Resistance in Late-Stage Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer Patients After First-Line Treatment with Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2025Review
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- IGF1R signaling induces epithelial-mesenchymal plasticity via ITGAV in cutaneous carcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Can Natural Products Targeting EMT Serve as the Future Anticancer Therapeutics?Molecules (Basel, Switzerland) · 2022Review
- Glucose-Restricted Diet Regulates the Tumor Immune Microenvironment and Prevents Tumor Growth in Lung Adenocarcinoma.Frontiers in oncology · 2022Article
- The role of IGF-pathway biomarkers in determining risks, screening, and prognosis in lung cancer.Oncotarget · 2022Review
- Silibinin Suppresses Tumor Cell-Intrinsic Resistance to Nintedanib and Enhances Its Clinical Activity in Lung Cancer.Cancers · 2021Article
- Lung Cancer Management with Silibinin: A Historical and Translational Perspective.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Review
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- TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target.Nature communications · 2020Article
- Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit mitochondrial respiration at complex I.Cell communication and signaling : CCS · 2020Article
- Inhibition of osteopontin overcomes acquired resistance to afatinib in EGFR-mutant non-small-cell lung cancer.Translational cancer research · 2020Article
- Understanding Lineage Plasticity as a Path to Targeted Therapy Failure inFrontiers in genetics · 2020Review
- IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse.Open medicine (Warsaw, Poland) · 2020Article
- Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts.Clinical & experimental metastasis · 2019Article
- When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?Frontiers in endocrinology · 2019Article
- An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer.International journal of biological sciences · 2019Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using non-small cell lung carcinoma (NSCLC) cells harboring the erlotinib-sensitizing Epidermal Growth Factor Receptor (EGFR) exon 19 mutation delE746-A750, we developed erlotinib-refractory derivatives in which hyperactive Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling associated with enrichment in epithelial-to-mesenchymal transition (EMT)-related morphological and transcriptional features. We then explored whether an IGF-1R/EMT crosstalk was sufficient to promote erlotinib refractoriness in the absence of second-site EGFR mutations, MET and AXL hyperactivation. Transforming Growth Factor-beta1 (TGFβ1)-induced mesenchymal trans-differentiation was sufficient to impede erlotinib functioning in the presence of drug-sensitive delE746-A750 EGFR mutation. Pharmacological blockade of IGF-1R fully prevented the TGFβ1's ability to activate an EMT protein signature [E-cadherin low/vimentin high]. The sole presence of erlotinib was capable of rapidly activate an IGF-1R-dependent, vimentin-enriched mesenchymal-like phenotype in delE746-A750-mutated epithelial cells. Even if transient, NSCLC cells' intrinsic plasticity to undergo crosstalk between IGF-1R and EMT signaling pathways can sufficiently eliminate the erlotinib-sensitizing effect of highly prevalent EGFR mutations and suggests the urgent need for dual IGF-1R/EMT-targeting strategies to circumvent erlotinib resistance.
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