ArticleMolecular cancer therapeutics2013
IGFBP2/FAK pathway is causally associated with dasatinib resistance in non-small cell lung cancer cells.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Rewiring the tumor microenvironment: IGFBP2 at the Nexus of remodeling and therapy resistance?Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 2026Article
- Association between four indirect indicators of insulin resistance and lung cancer: evidence from UK biobank and Mendelian randomization analysis.BMC cancer · 2026Article
- Article
- An integrated proteomic classifier to distinguish benign from malignant pulmonary nodules.Clinical proteomics · 2025Article
- [Progress in the Study of Mechanisms Clinically Relevant to Insulin Resistance and Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia.Experimental hematology & oncology · 2024Article
- The role of IGF-pathway biomarkers in determining risks, screening, and prognosis in lung cancer.Oncotarget · 2022Review
- Anticancer properties of dried-pericarp water extracts of Camellia japonica L. fermented with Aspergillus oryzae through regulation of IGFBP-2/mTOR pathway.Scientific reports · 2021Article
- Cabozantinib and dasatinib synergize to induce tumor regression in non-clear cell renal cell carcinoma.Cell reports. Medicine · 2021Article
- Novel Regulators of the IGF System in Cancer.Biomolecules · 2021Review
- Identification of novel transcription factor-microRNA-mRNA co-regulatory networks in pulmonary large-cell neuroendocrine carcinoma.Annals of translational medicine · 2021Article
- Uncovering the Anti-Lung-Cancer Mechanisms of the Herbal Drug FDY2004 by Network Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Association of Low Tumor Endothelial Cell pY397-Focal Adhesion Kinase Expression With Survival in Patients With Neoadjuvant-Treated Locally Advanced Breast Cancer.JAMA network open · 2020Article
- Regulation of β-catenin by IGFBP2 and its cytoplasmic actions in glioma.Journal of neuro-oncology · 2020Article
- Review
- Circular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and influence FAK phosphorylation.EBioMedicine · 2019Article
- Overexpression of IGFBP2 mRNA predicts poor survival in patients with glioblastoma.Bioscience reports · 2019Article
- Gene expression signature that predicts early molecular response failure in chronic-phase CML patients on frontline imatinib.Blood advances · 2019Article
- Article
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11 authors at 5 institutions in 2 countries.
Funding
Abstract
Insulin-like growth factor (IGF)-binding protein-2 (IGFBP2) expression is increased in various types of cancers, including in a subset of patients with lung cancer. Because IGFBP2 is involved in signal transduction of some critical cancer-related pathways, we analyzed the association between IGFBP2 and response to pathway-targeted agents in seven human non-small cell lung cancer (NSCLC) cell lines. Western blot analysis and ELISA showed that four of the seven NSCLC cell lines analyzed expressed high levels of IGFBP2, whereas the remaining three had barely detectable IGFBP2. Susceptibilities of those seven cell lines to nine anticancer agents targeting to IGF1R, Src, FAK, MEK, and AKT were determined by a dose-dependent cell viability assay. The results showed that high IGFBP2 levels were associated with resistance to dasatinib and, to a lesser degree, to sacaratinib, but not to other agents. Ectopic IGFBP2 overexpression or knockdown revealed that changing IGFBP2 expression levels reversed dasatinib susceptibility phenotype, suggesting a causal relationship between IGFBP2 expression and dasatinib resistance. Molecular characterization revealed that focal adhesion kinase (FAK) activation was associated with increased IGFBP2 expression and partially contributed to IGFBP2-mediated dasatinib resistance. Treatment with a combination of dasatinib and FAK inhibitor led to enhanced antitumor activity in IGFBP2-overexpressing and dasatinib-resistant NSCLC cells in vitro and in vivo. Our results showed that the IGFBP2/FAK pathway is causally associated with dasatinib resistance and may be used as biomarkers for identification of dasatinib responders among patients with lung cancer. Simultaneous targeting on Src and FAK will likely improve the therapeutic efficacy of dasatinib for treatment of lung cancer.
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