ArticleNeoplasia (New York, N.Y.)2020
An in vivo functional genomics screen of nuclear receptors and their co-regulators identifies FOXA1 as an essential gene in lung tumorigenesis.
Article in Neoplasia (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- ABCC2 as a novel therapeutic target in lung adenocarcinoma: a machine learning-driven discovery linking ammonia metabolism to prognosis and drug resistance.Journal of translational medicine · 2026Article
- Deciphering immune heterogeneity in lung adenocarcinoma via machine learning-based Differential Phenotype Immune Score: TPX2 as a key biomarker for immunotherapy resistance.Frontiers in immunology · 2026Article
- Acylation modification mediated post-translational modifications learning signature reveals ZDHHC18 promotes progression of lung adenocarcinoma by attenuating immunocyte activation.Frontiers in immunology · 2026Article
- Demystifying programmed cell death in lung adenocarcinoma: combined prognostic model construction.Translational cancer research · 2025Article
- Establishing a glycolysis-linked multigene prognostic signature in lung adenocarcinoma: a multicenter integrative approach.Journal of thoracic disease · 2025Article
- Targeting the FOXA1/BMI1 axis to overcome chemoresistance and suppress tumor progression in nasopharyngeal carcinoma.Cell death discovery · 2025Article
- BDNF is a prognostic biomarker involved in the immune infiltration of lung adenocarcinoma and associated with programmed cell death.Oncology letters · 2025Article
- Pan-cancer genomic analysis reveals FOXA1 amplification is associated with adverse outcomes in non-small cell lung, prostate, and breast cancers.Journal of the National Cancer Institute · 2025Article
- Identification of metabolism-associated molecular classification for effect and prognosis in lung adenocarcinoma based on multidatabases including the cancer genome atlas and gene expression omnibus.SAGE open medicine · 2025Article
- FeCell adhesion & migration · 2024Article
- Carcinogenic Role and Clinical Significance of Histone H3-H4 Chaperone Anti-silencing Function 1 B (ASF1B) in Lung Adenocarcinoma.Journal of Cancer · 2024Article
- Leveraging an immune cell signature to improve the survival and immunotherapy response of lung adenocarcinoma.Journal of Cancer · 2024Article
- Anoikis-related CTNND1 is associated with immuno-suppressive tumor microenvironment and predicts unfavorable immunotherapeutic outcome in non-small cell lung cancer.Journal of Cancer · 2024Article
- A Druggable FOXA1-Glucocorticoid Receptor Transcriptional Axis Drives Tumor Growth in a Subset of Non-Small Cell Lung Cancer.Cancer research communications · 2023Article
- Depiction of neuroendocrine features associated with immunotherapy response using a novel one-class predictor in lung adenocarcinoma.Discover oncology · 2023Article
- Identification of four metabolic subtypes and key prognostic markers in lung adenocarcinoma based on glycolytic and glutaminolytic pathways.BMC cancer · 2023Article
- Genomic and immunogenomic analysis of three prognostic signature genes in LUAD.BMC bioinformatics · 2023Article
- Genome instability-derived genes as a novel prognostic signature for lung adenocarcinoma.Frontiers in cell and developmental biology · 2023Article
- Establishment of a Lymph Node Metastasis-Associated Prognostic Signature for Lung Adenocarcinoma.Genetics research · 2023Article
- Comprehensive analysis of the FOXA1-related ceRNA network and identification of the MAGI2-AS3/DUSP2 axis as a prognostic biomarker in prostate cancer.Frontiers in oncology · 2023Article
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Using a mini-library of 1062 lentiviral shRNAs targeting 40 nuclear hormone receptors and 70 of their co-regulators, we searched for potential therapeutic targets that would be important during in vivo tumor growth using a parallel in vitro and in vivo shRNA screening strategy in the non-small cell lung cancer (NSCLC) line NCI-H1819. We identified 21 genes essential for in vitro growth, and nine genes specifically required for tumor survival in vivo, but not in vitro: NCOR2, FOXA1, HDAC1, RXRA, RORB, RARB, MTA2, ETV4, and NR1H2. We focused on FOXA1, since it lies within the most frequently amplified genomic region in lung adenocarcinomas. We found that 14q-amplification in NSCLC cell lines was a biomarker for FOXA1 dependency for both in vivo xenograft growth and colony formation, but not mass culture growth in vitro. FOXA1 knockdown identified genes involved in electron transport among the most differentially regulated, indicating FOXA1 loss may lead to a decrease in cellular respiration. In support of this, FOXA1 amplification was correlated with increased sensitivity to the complex I inhibitor phenformin. Integrative ChipSeq analyses reveal that FOXA1 functions in this genetic context may be at least partially independent of NKX2-1. Our findings are consistent with a neomorphic function for amplified FOXA1, driving an oncogenic transcriptional program. These data provide new insight into the functional consequences of FOXA1 amplification in lung adenocarcinomas, and identify new transcriptional networks for exploration of therapeutic vulnerabilities in this patient population.
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