ArticleThe Journal of clinical investigation2012
Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 167 citations in OpenAlex.
- Invasive mucinous adenocarcinoma of the lung: integrating molecular landscape, imaging phenotypes, and translational therapeutic strategies.Translational lung cancer research · 2026Review
- Functional Dissection of TP63 Dual-Promoter Regulatory Elements Reveals Context-Dependent Responsiveness to FOXA2, NKX2-1, SOX9, and TP63-Related Inputs.Current issues in molecular biology · 2026Article
- Prognostic Effect of TTF-1 Expression and Histopathology in the Patients with Advanced Lung Adenocarcinoma Treated with Immunochemotherapy.The Kobe journal of medical sciences · 2026Article
- NKX2-1 regulates cell survival, maturation, and DNAdamage responses as a cofactor of RUNX1 in T-cell acute lymphoblastic leukemia.Haematologica · 2026Article
- TTF-1 expression is associated with survival in patients with non-squamous non-small cell lung cancer treated with immune checkpoint inhibitor therapy.Molecular and clinical oncology · 2026Article
- The expression of PD-1 ligands in the immune microenvironment was altered in TTF-1-negative lung adenocarcinoma.Human cell · 2025Article
- Persistent lineage plasticity driving lung cancer development and progression.Clinical and translational medicine · 2025Review
- Prognostic analysis and development of a predictive model for pulmonary invasive mucinous adenocarcinoma.Journal of thoracic disease · 2025Article
- Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinoma.Molecular cell · 2025Article
- Nomogram model for the diagnosis of solitary nodular pulmonary mucinous adenocarcinoma.Scientific reports · 2024Article
- Ancestry-associated co-alteration landscape of KRAS and EGFR-altered non-squamous NSCLC.NPJ precision oncology · 2024Article
- Establishment and characterization of novel high mucus-producing lung tumoroids derived from a patient with pulmonary solid adenocarcinoma.Human cell · 2024Article
- Comparative study of imaging and pathology of primary mucinous adenocarcinoma with different imaging manifestations.The clinical respiratory journal · 2024Article
- Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration.Nature communications · 2023Article
- USP13 drives lung squamous cell carcinoma by switching lung club cell lineage plasticity.Molecular cancer · 2023Article
- Phosphorylated nuclear DICER1 promotes open chromatin state and lineage plasticity of AT2 tumor cells in lung adenocarcinomas.Science advances · 2023Article
- Tissue specificity of oncogenic BRAF targeted to lung and thyroid through a shared lineage factor.iScience · 2023Article
- Article
- FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung.Cancer research · 2023Article
- TTF-1 Expression and Clinical Outcomes of Combined Chemoimmunotherapy in Patients With Advanced Lung Adenocarcinoma: A Prospective Observational Study.JTO clinical and research reports · 2023Article
46 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 3 institutions in 2 countries.
Funding
Abstract
Mucinous adenocarcinoma of the lung is a subtype of highly invasive pulmonary tumors and is associated with decreased or absent expression of the transcription factor NK2 homeobox 1 (NKX2-1; also known as TTF-1). Here, we show that haploinsufficiency of Nkx2-1 in combination with oncogenic Kras(G12D), but not with oncogenic EGFR(L858R), caused pulmonary tumors in transgenic mice that were phenotypically similar to human mucinous adenocarcinomas. Gene expression patterns distinguished tumor goblet (mucous) cells from nontumorigenic airway and intestinal goblet cells. Expression of NKX2-1 inhibited urethane and oncogenic Kras(G12D)-induced tumorigenesis in vivo. Haploinsufficiency of Nkx2-1 enhanced Kras(G12D)-mediated tumor progression, but reduced EGFR(L858R)-mediated progression. Genome-wide analysis of gene expression demonstrated that a set of genes induced in mucinous tumors was shared with genes induced in a nontumorigenic chronic lung disease, while a distinct subset of genes was specific to mucinous tumors. ChIP with massively parallel DNA sequencing identified a direct association of NKX2-1 with the genes induced in mucinous tumors. NKX2-1 associated with the AP-1 binding element as well as the canonical NKX2-1 binding element. NKX2-1 inhibited both AP-1 activity and tumor colony formation in vitro. These data demonstrate that NKX2-1 functions in a context-dependent manner in lung tumorigenesis and inhibits Kras(G12D)-driven mucinous pulmonary adenocarcinoma.
Indexed as
Identifiers
What OpenQuestion holds
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.