ArticleGenes & development2015
Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
70 citing papers in PubMed, 99 citations in OpenAlex.
- Extracellular matrix-driven patient stratification and network modeling reveal distinct molecular grades with potential clinical implications.NPJ systems biology and applications · 2026Article
- Dual Effect ofBiology · 2026Article
- FOXA2 in cancer: from fundamental biology to clinical translation.Frontiers in oncology · 2026Review
- Evolution of Cancer Metastases via Lineage Trans-Differentiation.Research (Washington, D.C.) · 2026Article
- Long Non-Coding RNAs Contribute to Glucose Starvation-Induced Dedifferentiation in Lung Adenocarcinoma.Biomolecules · 2025Article
- Anoikis-related gene signatures predict prognosis of lung adenocarcinoma patients and reveal immune infiltration.Translational cancer research · 2024Article
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- Glucose Deprivation Promotes Pseudohypoxia and Dedifferentiation in Lung Adenocarcinoma.Cancer research · 2024Article
- HMGA2 promotes cancer metastasis by regulating epithelial-mesenchymal transition.Frontiers in oncology · 2024Review
- Prognostic and clinicopathological significance of FOXD1 in various cancers: a meta and bioinformation analysis.Future science OA · 2024Review
- The TRIM21-FOXD1-BCL-2 axis underlies hyperglycaemic cell death and diabetic tissue damage.Cell death & disease · 2023Article
- FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung.Cancer research · 2023Article
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- Oxidative stress-triggered Wnt signaling perturbation characterizes the tipping point of lung adeno-to-squamous transdifferentiation.Signal transduction and targeted therapy · 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
- CD44 Promotes Breast Cancer Metastasis through AKT-Mediated Downregulation of Nuclear FOXA2.Biomedicines · 2022Article
- FoxA1 and FoxA2 control growth and cellular identity in NKX2-1-positive lung adenocarcinoma.Developmental cell · 2022Article
- Histone H3K9 methyltransferase SETDB1 augments invadopodia formation to promote tumor metastasis.Oncogene · 2022Article
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10 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
12 authors at 4 institutions in 1 country.
Funding
Abstract
Despite the fact that the majority of lung cancer deaths are due to metastasis, the molecular mechanisms driving metastatic progression are poorly understood. Here, we present evidence that loss of Foxa2 and Cdx2 synergizes with loss of Nkx2-1 to fully activate the metastatic program. These three lineage-specific transcription factors are consistently down-regulated in metastatic cells compared with nonmetastatic cells. Knockdown of these three factors acts synergistically and is sufficient to promote the metastatic potential of nonmetastatic cells to that of naturally arising metastatic cells in vivo. Furthermore, silencing of these three transcription factors is sufficient to account for a significant fraction of the gene expression differences between the nonmetastatic and metastatic states in lung adenocarcinoma, including up-regulated expression of the invadopodia component Tks5long, the embryonal proto-oncogene Hmga2, and the epithelial-to-mesenchymal mediator Snail. Finally, analyses of tumors from a genetically engineered mouse model and patients show that low expression of Nkx2-1, Foxa2, and Cdx2 strongly correlates with more advanced tumors and worse survival. Our findings reveal that a large part of the complex transcriptional network in metastasis can be controlled by a small number of regulatory nodes that function redundantly, and loss of multiple nodes is required to fully activate the metastatic program.
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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.