ArticleThe Journal of clinical investigation2014
ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- A Systematic Review and Bioinformatics Study on Genes and micro-RNAs Involving the Transformation of Endometriosis into Ovarian Cancer.MicroRNA (Shariqah, United Arab Emirates) · 2020Pooled it
- Opsin3 regulates cell proliferation, migration, and apoptosis in lung adenocarcinoma via GPX3 pathway.European journal of medical research · 2025Article
- Dualistic role of ZEB1 and ZEB2 in tumor progression.Biology direct · 2025Review
- "Friends or foes": a new perspective of tumour metabolic transcriptional modification.Cell death & disease · 2025Review
- Review
- The transcription factor ZNF248 promotes colorectal cancer metastasis by binding to ZEB1.Journal of Cancer · 2024Article
- NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223.Journal of Cancer · 2024Article
- The p53/ZEB1-PLD3 feedback loop regulates cell proliferation in breast cancer.Cell death & disease · 2023Article
- EMT-activated secretory and endocytic vesicular trafficking programs underlie a vulnerability to PI4K2A antagonism in lung cancer.The Journal of clinical investigation · 2023Article
- Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer.Cancer gene therapy · 2023Article
- Targeting immunosuppressive Ly6C+ classical monocytes reverses anti-PD-1/CTLA-4 immunotherapy resistance.Frontiers in immunology · 2023Article
- Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling.Cellular & molecular immunology · 2022Article
- The role of the ZEB1-neuroinflammation axis in CNS disorders.Journal of neuroinflammation · 2022Review
- The microRNA-183/96/182 cluster inhibits lung cancer progression and metastasis by inducing an interleukin-2-mediated antitumor CD8Genes & development · 2022Article
- Transcriptional control of a collagen deposition and adhesion process that promotes lung adenocarcinoma growth and metastasis.JCI insight · 2022Article
- Zeb1 induces immune checkpoints to form an immunosuppressive envelope around invading cancer cells.Science advances · 2021Article
- Elastic Net Models Based on DNA Copy Number Variations Predicts Clinical Features, Expression Signatures, and Mutations in Lung Adenocarcinoma.Frontiers in genetics · 2021Article
- USP43 directly regulates ZEB1 protein, mediating proliferation and metastasis of colorectal cancer.Journal of Cancer · 2021Article
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
- Zeb1 promotes corneal neovascularization by regulation of vascular endothelial cell proliferation.Communications biology · 2020Article
18 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 5 institutions in 2 countries.
Funding
Abstract
Epithelial tumor cells that have undergone epithelial-to-mesenchymal transition (EMT) are typically prone to metastasis and drug resistance and contribute to a poor clinical outcome. The transcription factor ZEB1 is a known driver of EMT, and mediators of ZEB1 represent potential therapeutic targets for metastasis suppression. Here, we have shown that phosphatidylinositol 3-kinase-targeted (PI3K-targeted) therapy suppresses metastasis in a mouse model of Kras/Tp53-mutant lung adenocarcinoma that develops metastatic disease due to high expression of ZEB1. In lung adenocarcinoma cells from Kras/Tp53-mutant animals and human lung cancer cell lines, ZEB1 activated PI3K by derepressing miR-200 targets, including amphiregulin (AREG), betacellulin (BTC), and the transcription factor GATA6, which stimulated an EGFR/ERBB2 autocrine loop. Additionally, ZEB1-dependent derepression of the miR-200 and miR-183 target friend of GATA 2 (FOG2) enhanced GATA3-induced expression of the p110α catalytic subunit of PI3K. Knockdown of FOG2, p110α, and RHEB ameliorated invasive and metastatic propensities of tumor cells. Surprisingly, FOG2 was not required for mesenchymal differentiation, suggesting that mesenchymal differentiation and invasion are distinct and separable processes. Together, these results indicate that ZEB1 sensitizes lung adenocarcinoma cells to metastasis suppression by PI3K-targeted therapy and suggest that treatments to selectively modify the metastatic behavior of mesenchymal tumor cells are feasible and may be of clinical value.
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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.