ArticleThe Journal of biological chemistry2012
Occludin is a direct target of thyroid transcription factor-1 (TTF-1/NKX2-1).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Trial
- Next Decade Research in Asthma: Broad Omics-Based Exploration Versus Targeted Airway Epithelium Studies.Journal of clinical medicine · 2025Review
- The expression of PD-1 ligands in the immune microenvironment was altered in TTF-1-negative lung adenocarcinoma.Human cell · 2025Article
- Identifying behavior regulatory leverage over mental disorders transcriptomic network hubs toward lifestyle-dependent psychiatric drugs repurposing.Human genomics · 2025Article
- PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.Acta biochimica et biophysica Sinica · 2023Article
- Review
- Deciphering an isolated lung phenotype of NKX2-1 frameshift pathogenic variant.Frontiers in pediatrics · 2022Article
- Particulate matter disrupts airway epithelial barrier via oxidative stress to promoteJournal of thoracic disease · 2019Article
- Mechanistic Study of TTF-1 Modulation of Cellular Sensitivity to Cisplatin.Scientific reports · 2019Article
- Tumor Suppressor Activity of Selenbp1, a Direct Nkx2-1 Target, in Lung Adenocarcinoma.Molecular cancer research : MCR · 2018Article
- Transgenic up-regulation of Claudin-6 decreases fine diesel particulate matter (DPM)-induced pulmonary inflammation.Environmental science and pollution research international · 2018Article
- Immunohistochemical Biomarkers in Thyroid Pathology.Endocrine pathology · 2018Review
- NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.Thyroid : official journal of the American Thyroid Association · 2018Article
- Thyroid transcription factor 1 enhances cellular statin sensitivity via perturbing cholesterol metabolism.Oncogene · 2018Article
- Roles of Thyroid Transcription Factor 1 in Lung Cancer Biology.Vitamins and hormones · 2018Review
- NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer.BMC pulmonary medicine · 2017Article
- MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients.Frontiers in physiology · 2017Article
- Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation.International journal of environmental research and public health · 2016Article
- Detection of Novel Gene Variants Associated with Congenital Hypothyroidism in a Finnish Patient Cohort.Thyroid : official journal of the American Thyroid Association · 2016Article
- The MicroRNA 29 Family Promotes Type II Cell Differentiation in Developing Lung.Molecular and cellular biology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The thyroid transcription factor 1 gene (TTF-1 or NKX2-1) is essential to lung development; however, it is also a critical factor in lung cancer. TTF-1 is amplified in lung cancers, suggesting that it is a gain-of-function lung oncogene. Conversely, TTF-1 counters epithelial to mesenchymal transition in cell-based studies and inhibits progression of primary lung adenocarcinomas to metastases in an animal model of lung adenocarcinomas. The unifying theory regarding TTF-1 is that it exhibits both pro-oncogenic and anti-metastatic function depending on the cellular context. Occludin is the first discovered constituent of the epithelial tight junction; in recent years, a functional role of occludin as a tumor suppressor has begun to emerge. Here, we demonstrate that TTF-1 transactivated the expression of the epithelial tight junction molecules occludin (OCLN) and claudin-1 (CLDN1). We show that transcriptional activation occurred through a direct interaction of TTF-1 with the OCLN and CLDN1 promoters. Furthermore, in cells that lack TTF-1, exogenous TTF-1 expression dampened the inhibitory effect of TGF-β on occludin and claudin-1 content. Using cells derived from a genetically engineered mouse model of lung adenocarcinomas, we observed that silenced TTF-1 expression down-regulated occludin, which we supported with additional siRNA experiments. Finally, TTF-1 knockdown conferred human lung cancer cells resistance to anoikis, and expression of occludin restored cellular sensitivity to anoikis. Overexpression of occludin impeded migration and induced anoikis in lung carcinoma cells. Collectively, these data suggest that TTF-1 transcriptionally regulates occludin, which represents another avenue of TTF-1-mediated metastasis suppression.
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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.