ArticleThe Journal of clinical investigation2016
ZEB1 drives epithelial-to-mesenchymal transition in lung cancer.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
198 citing papers in PubMed, 1 synthesis or guideline pooled it, 343 citations in OpenAlex.
- Heavy metal carcinogenicity: a scoping review of observational & experimental evidence.Frontiers in oncology · 2025Pooled it
- Deciphering the Role of ZEB1 as a Central Regulator of Epithelial-Mesenchymal Transition and Hormonal Resistance in Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Zeb1 Is a Determinant of EMT in Human MDA-MB-231 Breast Cancer Cells and M13-MDA231 Tumor Hybrids.International journal of molecular sciences · 2026Article
- SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma.Translational oncology · 2026Article
- Early cell-autonomous and niche-mediated epithelial response to influenza infection in primary alveolar organoids.JCI insight · 2026Article
- Epithelial-mesenchymal transition and immunosuppression: Two sides of the same coin.Cellular and molecular life sciences : CMLS · 2026Review
- Early-stage multi-cancer detection through a plasma extracellular vesicle protein signature.Cell reports. Medicine · 2026Article
- THY1Nature cell biology · 2026Article
- GLCCI1 alleviates airway remodeling in asthmatic mice by inhibiting ZEB1-mediated epithelial-mesenchymal transition.Respiratory research · 2026Article
- The role of homeobox genes in signaling pathway positive feedback loops and cancer therapy.Frontiers in oncology · 2026Article
- Early cell autonomous and niche-mediated alveolar epithelial response to influenza infection in primary lung organoids.bioRxiv : the preprint server for biology · 2025Article
- Harnessing the role of transforming growth factor-β in glioblastoma: a focus on phytochemicals.Medical oncology (Northwood, London, England) · 2025Review
- Unraveling the molecular-pathological characteristics and cellular complexity of the tumor immune microenvironment in metastatic non-small cell lung cancer.Cell communication and signaling : CCS · 2025Review
- Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins.Molecular therapy. Nucleic acids · 2025Article
- Therapeutic effect of Chelidonium majus hydro-alcoholic extract alone and in combination with oxaliplatin on ovarian cancer cell line.Discover oncology · 2025Article
- Longitudinal pharmacogenomic analysis of refractory lung cancer to identify therapeutic candidates for epidermal growth factor receptor-tyrosine kinase inhibitor resistance subclones.Experimental & molecular medicine · 2025Article
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- CYP24A1 Binding to FUS Maintains Tumor Properties by Regulating the miR-200c/ZEB1/EMT Axis.Cancer science · 2025Article
138 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
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Increased expression of zinc finger E-box binding homeobox 1 (ZEB1) is associated with tumor grade and metastasis in lung cancer, likely due to its role as a transcription factor in epithelial-to-mesenchymal transition (EMT). Here, we modeled malignant transformation in human bronchial epithelial cells (HBECs) and determined that EMT and ZEB1 expression are early, critical events in lung cancer pathogenesis. Specific oncogenic mutations in TP53 and KRAS were required for HBECs to engage EMT machinery in response to microenvironmental (serum/TGF-β) or oncogenetic (MYC) factors. Both TGF-β- and MYC-induced EMT required ZEB1, but engaged distinct TGF-β-dependent and vitamin D receptor-dependent (VDR-dependent) pathways, respectively. Functionally, we found that ZEB1 causally promotes malignant progression of HBECs and tumorigenicity, invasion, and metastases in non-small cell lung cancer (NSCLC) lines. Mechanistically, ZEB1 expression in HBECs directly repressed epithelial splicing regulatory protein 1 (ESRP1), leading to increased expression of a mesenchymal splice variant of CD44 and a more invasive phenotype. In addition, ZEB1 expression in early stage IB primary NSCLC correlated with tumor-node-metastasis stage. These findings indicate that ZEB1-induced EMT and associated molecular changes in ESRP1 and CD44 contribute to early pathogenesis and metastatic potential in established lung cancer. Moreover, TGF-β and VDR signaling and CD44 splicing pathways associated with ZEB1 are potential EMT chemoprevention and therapeutic targets in NSCLC.
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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.