ArticleOncotarget2017
Interaction between the estrogen receptor and fibroblast growth factor receptor pathways in non-small cell lung cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.PloS one · 2025Article
- Two-level Bayesian interaction analysis for survival data incorporating pathway information.Biometrics · 2023Article
- New Perspectives on Sex Steroid Hormones Signaling in Cancer-Associated Fibroblasts of Non-Small Cell Lung Cancer.Cancers · 2023Review
- Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment.Cancers · 2022Review
- Increased serum concentrations of estrogen-induced growth factors Midkine and FGF2 in NF1 patients with plexiform neurofibroma.American journal of translational research · 2022Article
- MicroRNA-155-5p promotes cell proliferation and invasion in lung squamous cell carcinoma through negative regulation of fibroblast growth factor 9 expression.Journal of thoracic disease · 2021Article
- Regulation of aromatase in cancer.Molecular and cellular biochemistry · 2021Review
- Syngeneic tobacco carcinogen-induced mouse lung adenocarcinoma model exhibits PD-L1 expression and high tumor mutational burden.JCI insight · 2021Article
- Digit ratio (2D:4D) in women and men with lung cancer.Scientific reports · 2020Observational
- Aggressive pulmonary adenocarcinoma with new FGFR translocation and cMET mutation not responsive to crizotinib and nintedanib treatment: a case report.Translational cancer research · 2020Article
- Involvement of the Estrogen and Progesterone Axis in Cancer Stemness: Elucidating Molecular Mechanisms and Clinical Significance.Frontiers in oncology · 2020Review
- Influence of Estrogen on the NSCLC Microenvironment: A Comprehensive Picture and Clinical Implications.Frontiers in oncology · 2020Review
- Estrogen receptors promote NSCLC progression by modulating the membrane receptor signaling network: a systems biology perspective.Journal of translational medicine · 2019Article
- Article
- FGF2 and FGFR2 in patients with idiopathic pulmonary fibrosis and lung cancer.Oncology letters · 2018Article
- Establishment of lung cancer patient-derived xenograft models and primary cell lines for lung cancer study.Journal of translational medicine · 2018Article
- Preclinical Evidence for Combined Use of Aromatase Inhibitors and NSAIDs as Preventive Agents of Tobacco-Induced Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2018Article
- The Role of the Estrogen Pathway in the Tumor Microenvironment.International journal of molecular sciences · 2018Review
- Estrogen, Estrogen Receptor and Lung Cancer.International journal of molecular sciences · 2017Review
- [Recent Advances in Association of Estrogen and Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2017Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog. Mice administered β-estradiol during carcinogen exposure showed increased FGF2, FGF9, SOX2, and Nanog expression in airway preneoplasias. In normal FGFR1 copy number NSCLC cell lines, multiple FGFR receptors were expressed and secreted several FGFs. β-estradiol caused enhanced FGF2 release, which was blocked by fulvestrant. Upon co-inhibition of ER and FGFRs using fulvestrant and the pan-FGFR inhibitor AZD4547, phosphorylation of FRS2, the FGFR docking protein, was maximally reduced, and enhanced anti-proliferative effects were observed. Combined AZD4547 and fulvestrant enhanced lung tumor xenograft growth inhibition and decreased Ki67 and stem cell marker expression. To verify a link between ERβ, the predominant ER in NSCLC, and FGFR signaling in patient tumors, mRNA analysis was performed comparing high versus low ERβ expressing tumors. The top differentially expressed genes in high ERβ tumors involved FGF signaling and human embryonic stem cell pluripotency. These results suggest interaction between the ER and FGFR pathways in NSCLC promotes a stem-like state. Combined FGFR and ER inhibition may increase the efficacy of FGFR inhibitors for NSCLC patients lacking FGFR genetic alterations.
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