ArticleClinical & experimental metastasis2008
Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy.
Article in Clinical & experimental metastasis, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01480141 (A Therapeutic Trial of Afatinib in the Neoadjuvant Setting. Molecular Effects of Afatinib), which is not on this map. Cited by 110 papers.
What it found
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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.
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.
A Therapeutic Trial of Afatinib in the Neoadjuvant Setting. Molecular Effects of Afatinib: A Window of Opportunity Trial In Early Stage NSCLC
Who cites it
110 citing papers in PubMed, 191 citations in OpenAlex.
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- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- mTORC2-driven chromatin cGAS mediates chemoresistance through epigenetic reprogramming in colorectal cancer.Nature cell biology · 2024Article
- Voltage-gated sodium channels in cancers.Biomarker research · 2024Review
- Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance.International journal of molecular sciences · 2024Review
- Biphasic function of GSK3β in gefitinib‑resistant NSCLC with or without EGFR mutations.Experimental and therapeutic medicine · 2023Article
- Mass Spectrometry and Pharmacological Approaches to Measuring Cooption and Reciprocal Activation of Receptor Tyrosine Kinases.Proteomes · 2023Article
- Network motifs and hypermotifs in TGFβ-induced epithelial to mesenchymal transition and metastasis.Frontiers in systems biology · 2023Article
- Recent and Future Strategies to Overcome Resistance to Targeted Therapies and Immunotherapies in Metastatic Colorectal Cancer.Journal of clinical medicine · 2022Review
- PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis.BMC cancer · 2022Article
- Diagnostic, Predictive, and Prognostic Biomarkers in Non-Small Cell Lung Cancer (NSCLC) Management.Journal of personalized medicine · 2021Review
- Therapeutic Targeting of Cancer Stem Cells in Lung, Head and Neck, and Bladder Cancers.Cancers · 2021Review
- Chemotherapy confers a conserved secondary tolerance to EGFR inhibition via AXL-mediated signaling bypass.Scientific reports · 2021Article
- Analysis of Single Nucleotide Variants (SNVs) Induced by Exposure to PMInternational journal of environmental research and public health · 2021Article
- Identification of Phospho-Tyrosine Targets as a Strategy for the Treatment of Esophageal Adenocarcinoma Cells.OncoTargets and therapy · 2021Article
- Partial EMT in Squamous Cell Carcinoma: A Snapshot.International journal of biological sciences · 2021Review
- 2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.Journal of oncology · 2021Review
- Endogenous Anti-Cancer Candidates in GPCR, ER Stress, and EMT.Biomedicines · 2020Review
- Article
- Revisiting a controversy: The effect of EGF on EGFR dimer stability.Biochimica et biophysica acta. Biomembranes · 2020Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NSCLC cells with a mesenchymal phenotype have shown a marked reduction in sensitivity to EGFR inhibitors, though the molecular rationale has remained obscure. Here we find that in mesenchymal-like tumor cells both tyrosine phosphorylation of EGFR, ErbB2, and ErbB3 signaling networks and expression of EGFR family ligands were decreased. While chronic activation of EGFR can promote an EMT-like transition, once having occurred EGFR family signaling was attenuated. We investigated the mechanisms by which mesenchymal-like cells bypass EGFR signaling and acquire alternative routes of proliferative and survival signaling. Mesenchymal-like NSCLC cells exhibit aberrant PDGFR and FGFR expression and autocrine signaling through these receptors can activate the MEK-ERK and PI3K pathways. Selective pharmacological inhibition of PDGFR or FGFR receptor tyrosine kinases reduced cell proliferation in mesenchymal-like but not epithelial NSCLC cell lines. A metastable, reversible EMT-like transition in the NSCLC line H358 was achieved by exogenous TGFbeta, which served as a model EMT system. The H358/TGFbeta cells showed many of the attributes of established mesenchymal-like NSCLC cells including a loss of cell-cell junctions, a loss of EGF-family ligand expression, a loss of ErbB3 expression, increased EGFR-independent Mek-Erk pathway activation and reduced sensitivity to EGFR inhibition. Notably an EMT-dependent acquisition of PDGFR, FGFR and TGFbeta receptors in H358/TGFbeta cells was also observed. In H358/TGFbeta cells both PDGFR and FGFR showed functional ligand stimulation of their intrinsic tyrosine kinase activities. The findings of kinase switching and acquired PDGFR and FGFR signaling suggest investigation of new inhibitor combinations to target NSCLC metastases.
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Registered trials
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.