ArticlePloS one2015
Integrative Genomics Implicates EGFR as a Downstream Mediator in NKX2-1 Amplified Non-Small Cell Lung Cancer.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Androgen receptor may promote tumor progression via TTF-1/EGFR pathway in metastatic nasopharyngeal carcinoma.Translational oncology · 2026Article
- NKX2‑1 copy number alterations are associated with oncogenic, immunological and prognostic remodeling in non‑small cell lung cancer.Oncology letters · 2024Article
- Thyroid transcription factor 1 (TTF-1) negativity as a predictor of unfavorable response to EGFR-TKI therapy in advanced lung adenocarcinoma patients with EGFR mutations.Thoracic cancer · 2023Article
- Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer.Journal of clinical medicine · 2022Article
- Review
- Thyroid Transcription Factor-1: Structure, Expression, Function and Its Relationship with Disease.BioMed research international · 2021Review
- [Clinical Value of Cerebrospinal Fluid ctDNA in Patients with Non-small Cell Lung Cancer Meningeal Metastasis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Article
- Serum microRNA-365 suppresses non-small-cell lung cancer metastasis and invasion in patients with bone metastasis of lung cancer.The Journal of international medical research · 2020Article
- An in vivo functional genomics screen of nuclear receptors and their co-regulators identifies FOXA1 as an essential gene in lung tumorigenesis.Neoplasia (New York, N.Y.) · 2020Article
- Comparative analysis of TTF-1 binding DNA regions in small-cell lung cancer and non-small-cell lung cancer.Molecular oncology · 2020Article
- Thyroid transcription factor-1 as a prognostic indicator for stage IV lung adenocarcinoma with and without EGFR-sensitizing mutations.BMC cancer · 2019Article
- Mechanistic Study of TTF-1 Modulation of Cellular Sensitivity to Cisplatin.Scientific reports · 2019Article
- The Relationship between Nkx2.1 and DNA Oxidative Damage Repair in Nickel Smelting Workers: Jinchang Cohort Study.International journal of environmental research and public health · 2019Article
- Tumor Suppressor Activity of Selenbp1, a Direct Nkx2-1 Target, in Lung Adenocarcinoma.Molecular cancer research : MCR · 2018Article
- Roles of Thyroid Transcription Factor 1 in Lung Cancer Biology.Vitamins and hormones · 2018Review
- NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer.BMC pulmonary medicine · 2017Article
- Thyroid Transcription Factor 1 Reprograms Angiogenic Activities of Secretome.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NKX2-1, encoding a homeobox transcription factor, is amplified in approximately 15% of non-small cell lung cancers (NSCLC), where it is thought to drive cancer cell proliferation and survival. However, its mechanism of action remains largely unknown. To identify relevant downstream transcriptional targets, here we carried out a combined NKX2-1 transcriptome (NKX2-1 knockdown followed by RNAseq) and cistrome (NKX2-1 binding sites by ChIPseq) analysis in four NKX2-1-amplified human NSCLC cell lines. While NKX2-1 regulated genes differed among the four cell lines assayed, cell proliferation emerged as a common theme. Moreover, in 3 of the 4 cell lines, epidermal growth factor receptor (EGFR) was among the top NKX2-1 upregulated targets, which we confirmed at the protein level by western blot. Interestingly, EGFR knockdown led to upregulation of NKX2-1, suggesting a negative feedback loop. Consistent with this finding, combined knockdown of NKX2-1 and EGFR in NCI-H1819 lung cancer cells reduced cell proliferation (as well as MAP-kinase and PI3-kinase signaling) more than knockdown of either alone. Likewise, NKX2-1 knockdown enhanced the growth-inhibitory effect of the EGFR-inhibitor erlotinib. Taken together, our findings implicate EGFR as a downstream effector of NKX2-1 in NKX2-1 amplified NSCLC, with possible clinical implications, and provide a rich dataset for investigating additional mediators of NKX2-1 driven oncogenesis.
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