ArticleOncogene2017
TTF-1/NKX2-1 binds to DDB1 and confers replication stress resistance to lung adenocarcinomas.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- NKX2-1 regulates cell survival, maturation, and DNAdamage responses as a cofactor of RUNX1 in T-cell acute lymphoblastic leukemia.Haematologica · 2026Article
- Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinoma.Molecular cell · 2025Article
- A Small Molecule Targeting the Intracellular Tyrosine Kinase Domain of ROR1 (KAN0441571C) Induced Significant Apoptosis of Non-Small Cell Lung Cancer (NSCLC) Cells.Pharmaceutics · 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
- A transcriptomic signature for prostate cancer relapse prediction identified from the differentially expressed genes between TP53 mutant and wild-type tumors.Scientific reports · 2022Article
- Inhibition of heat shock protein 90 destabilizes receptor tyrosine kinase ROR1 in lung adenocarcinoma.Cancer science · 2021Article
- The correlation of WDR76 expression with survival outcomes and immune infiltrates in lung adenocarcinoma.PeerJ · 2021Article
- Thyroid Transcription Factor-1: Structure, Expression, Function and Its Relationship with Disease.BioMed research international · 2021Review
- MNX1 Promotes Malignant Progression of Cervical Cancer via Repressing the Transcription of p21Frontiers in oncology · 2020Article
- Role of Damage DNA-Binding Protein 1 in Pancreatic Cancer Progression and Chemoresistance.Cancers · 2019Article
- Basal CHK1 activity safeguards its stability to maintain intrinsic S-phase checkpoint functions.The Journal of cell biology · 2019Article
- Two distinct E3 ligases, SCFFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Mechanistic Study of TTF-1 Modulation of Cellular Sensitivity to Cisplatin.Scientific reports · 2019Article
- PITX2 enhances progression of lung adenocarcinoma by transcriptionally regulating WNT3A and activating Wnt/β-catenin signaling pathway.Cancer cell international · 2019Article
- Is Benign Hereditary Chorea Really Benign? Brain-Lung-Thyroid Syndrome Caused byMovement disorders clinical practice · 2019Article
- Thyroid transcription factor 1 enhances cellular statin sensitivity via perturbing cholesterol metabolism.Oncogene · 2018Article
- TTF-1 and EGFR expression are related to EGFR mutation in lung adenocarcinoma.International journal of clinical and experimental pathology · 2018Article
- Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients.Gastroenterology · 2018Review
- Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma.Oncotarget · 2017Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TTF-1, also known as NKX2-1, is a transcription factor that has indispensable roles in both lung development and physiology. We and others have reported that TTF-1 frequently exhibits high expression with increased copy number in lung adenocarcinomas, and also has a role as a lineage-survival oncogene through transcriptional activation of crucial target genes including ROR1 and LMO3. In the present study, we employed a global proteomic search for proteins that interact with TTF-1 in order to provide a more comprehensive picture of this still enigmatic lineage-survival oncogene. Our results unexpectedly revealed a function independent of its transcriptional activity, as TTF-1 was found to interact with DDB1 and block its binding to CHK1, which in turn attenuated ubiquitylation and subsequent degradation of CHK1. Furthermore, TTF-1 overexpression conferred resistance to cellular conditions under DNA replication stress (RS) and prevented an increase in consequential DNA double-strand breaks, as reflected by attenuated induction of pCHK2 and γH2AX. Our findings suggest that the novel non-transcriptional function of TTF-1 identified in this study may contribute to lung adenocarcinoma development by conferring tolerance to DNA RS, which is known to be inherently elicited by activation of various oncogenes.
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