Affinage

TTF1

Transcription termination factor 1 · UniProt Q15361

Length
905 aa
Mass
103.1 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TTF-1 (NKX2-1) is a homeodomain transcription factor that establishes and maintains lineage-specific gene programs in lung epithelium, thyroid follicular cells, and hypothalamic neurons by binding defined promoter/enhancer elements in target genes (PMID:18487360, PMID:8062273, PMID:11161473). In the lung it directly drives surfactant and epithelial differentiation genes—activating SP-A, SP-B, and SP-C promoters, the α5 nicotinic acetylcholine receptor subunit, and (with FoxA2 and Gata-6) Claudin-6—with a TTF-1 binding element being necessary for cell-specific, developmental, and hormonal regulation of surfactant gene expression in vivo (PMID:18487360, PMID:16461352, PMID:21143907, PMID:24970044), and is required for branching morphogenesis of the developing airway (PMID:8612983). Its transcriptional output is tuned through physical interactions with coactivators TAZ, CBP/p300, SRC-1, and PARP-1/2, and through PKA-mediated phosphorylation and subsequent acetylation that enhance its DNA binding (PMID:14970209, PMID:11713256, PMID:16461352). In thyroid cells TTF-1 cooperates synergistically with PAX8 to activate thyroglobulin, thyroperoxidase, and NIS, an interaction whose loss in disease-associated mutants abolishes activation (PMID:15872358, PMID:19336474, PMID:24712572). TTF-1 functions in cancer as a lineage dependency: TTF-1-expressing lung adenocarcinoma lines require it for survival (PMID:17616654), while in small cell lung cancer its expression is driven by BRN2 and it cooperates with ASCL1 at neuroendocrine and Bcl-2 family loci to support an antiapoptotic neuroendocrine program (PMID:23358112, PMID:31782890). It also suppresses tumor cell motility and metastasis by transactivating MYBPH, which directly binds and inhibits ROCK1 (PMID:22085929). Conditional neuronal deletion in mice impairs female reproductive maturation, reflecting TTF-1 control of hypothalamic pro-reproductive genes including LHRH, erbB-2, and preproenkephalin (PMID:17182767, PMID:11161473). A human TTF-1/NKX2-1 missense mutation underlies brain-lung-thyroid syndrome through loss of transactivation capacity (PMID:19336474).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 Low

    Established that TTF-1, alongside PAX-8, is associated with the differentiated thyroid phenotype and activation of thyroid-specific promoters, framing it as a thyroid lineage factor.

    Evidence mRNA quantification, immunohistochemistry, and referenced promoter assays in thyroid carcinomas

    PMID:8062273

    Open questions at the time
    • Promoter activation claims referenced rather than newly demonstrated here
    • TTF-1+PAX-8 alone insufficient to drive full differentiated phenotype
    • no direct binding data in this study
  2. 1995 Medium

    Loss-of-function showed TTF-1 is required for lung airway morphogenesis and for thyroid cell proliferation, establishing it as a developmental driver in both lineages.

    Evidence Antisense oligonucleotide suppression in mouse lung explants and in FRTL-5 thyroid cells with proliferation readouts

    PMID:7559458 PMID:8612983

    Open questions at the time
    • Antisense specificity limited to single lab
    • direct transcriptional targets mediating morphogenesis not defined
    • thyroid proliferation effect placed in cAMP/PKA pathway but downstream targets unresolved
  3. 1998 Medium

    Demonstrated that TTF-1 and PAX-8 are jointly required, neither alone sufficient, to restore thyroglobulin promoter activity in deficient thyroid carcinoma cells, defining a cooperative thyroid program.

    Evidence Tg promoter reporter rescue by co-transfection in ARO/WRO cells with RT-PCR

    PMID:9854590

    Open questions at the time
    • Single assay type
    • physical basis of cooperation not addressed
    • lineage restriction mechanism unexplained
  4. 2001 Medium

    Identified post-translational and coactivator control of TTF-1, showing PKA phosphorylation promotes CBP/SRC-1 interaction and acetylation to enhance DNA binding, and that hypothalamic TTF-1 transactivates reproductive promoters.

    Evidence Pull-down, immunodepletion, reporter assays with PKA/E1A manipulation (SP-A); in situ hybridization and promoter transactivation (hypothalamus)

    PMID:11161473 PMID:11713256

    Open questions at the time
    • Acetyltransferase responsible not pinned to a single enzyme
    • phosphosite mapping incomplete
    • in vivo relevance of hypothalamic targets not yet genetically tested
  5. 2004 Medium

    Expanded the TTF-1 coactivator repertoire and target range, showing TAZ binds its N-terminus to synergize on SP-C and that TTF-1 regulates the RET promoter at HSCR-associated variants.

    Evidence Mammalian two-hybrid, GST pull-down, deletion mapping, SP-C reporter (TAZ); RET promoter reporters with patient mutation and IHC co-expression

    PMID:14970209 PMID:15548547

    Open questions at the time
    • TAZ interaction validated in reporter context only
    • RET regulation in enteric development not shown in vivo
    • Gly322Ser mechanism limited to reporter readout
  6. 2006 High

    Confirmed PARP-1/2 as physical partners enhancing SP-B activation, and a neuron-specific genetic knockout established TTF-1's causal role in female reproductive maturation.

    Evidence Endogenous co-IP with MS and domain mapping (PARP-2); conditional Cre-lox Ttf1 deletion with hormonal/behavioral phenotyping plus primate expression profiling

    PMID:16461352 PMID:17182767

    Open questions at the time
    • PARP enzymatic vs scaffolding contribution to SP-B activation unresolved
    • specific hypothalamic target gene driving phenotype not isolated genetically
  7. 2007 Medium

    Defined TTF-1 as a lineage-survival dependency in lung adenocarcinoma, since RNAi knockdown selectively killed TTF-1-expressing tumor lines.

    Evidence RNAi knockdown, viability/apoptosis assays, FISH in patient samples

    PMID:17616654

    Open questions at the time
    • Downstream survival effectors not identified here
    • single-lab cell line panel
    • mechanism of selective dependency unexplained
  8. 2008 High

    Transgenic mutagenesis proved the TTF-1 binding element is necessary in vivo for developmental and hormonal regulation of a surfactant gene, moving beyond cell-culture correlation.

    Evidence Transgenic mouse reporter with site-directed TBE mutation and hormonal lung explant treatments

    PMID:18487360

    Open questions at the time
    • Single target promoter tested
    • coactivators required in vivo not defined
    • developmental timing mechanism not dissected
  9. 2009 Medium

    Linked TTF-1/NKX2-1 missense mutations to brain-lung-thyroid syndrome and showed PAX8 can rescue some but not all mutant deficits, mechanistically connecting the TTF-1–PAX8 interaction to disease.

    Evidence Transactivation reporter assays with PAX8 co-transfection and patient mutation analysis

    PMID:19336474

    Open questions at the time
    • Structural basis of differential PAX8 rescue unresolved
    • lung/brain phenotype correlation not assayed at promoter level
    • single lab
  10. 2011 High

    Resolved a metastasis-suppressive mechanism and a cytokine control loop: TTF-1 activates MYBPH which inhibits ROCK1, and TNF-α suppresses TTF-1 transcription at its own promoter.

    Evidence ChIP, reporter, reciprocal co-IP and kinase assays with migration/metastasis models (MYBPH-ROCK1); EMSA, ChIP, mutagenesis, reporter with TNF-α treatment (promoter regulation)

    PMID:21784970 PMID:22085929

    Open questions at the time
    • Whether MYBPH axis operates across all TTF-1 tumor contexts unknown
    • TNF-α effect on Sp1 phosphorylation mechanism partial
    • in vivo metastasis suppression generalization untested
  11. 2013 High

    Defined the upstream driver of TTF-1 in small cell lung cancer, showing BRN2 binds and activates the TTF-1 isoform 2 promoter as a context-specific regulatory input.

    Evidence Reporter assays, siRNA knockdown, ChIP, bisulfite sequencing, IHC in SCLC

    PMID:23358112

    Open questions at the time
    • Why SCLC uses BRN2-driven isoform 2 specifically unresolved
    • functional consequence of BRN2-driven TTF-1 for SCLC biology not fully tested here
  12. 2014 Medium

    Showed context-dependent TTF-1 target reprogramming and pathway placement: it cooperates with FoxA2/Gata-6 on Claudin-6, and lies downstream of mTOR and upstream of NIS in thyroid redifferentiation.

    Evidence Reporter assays and co-localization (Cldn6); mTOR inhibitor treatment with TTF-1 siRNA rescue and iodine uptake (NIS)

    PMID:24712572 PMID:24970044

    Open questions at the time
    • Direct vs indirect mTOR-to-TTF-1 link not defined
    • Cldn6 combinatorial logic in vivo not tested
    • single-lab assays
  13. 2019 High

    Genome-wide mapping revealed TTF-1's cistrome is rewired between tumor lineages, with SCLC-specific E-box sites and cooperative co-occupancy with ASCL1 driving an antiapoptotic neuroendocrine program.

    Evidence ChIP-seq, RNA-seq, and co-occupancy analysis comparing SCLC and adenocarcinoma lines

    PMID:31782890

    Open questions at the time
    • Mechanism setting lineage-specific binding (chromatin state) not defined
    • ASCL1-TTF-1 physical interaction not directly shown
    • Bcl-2 regulation directness untested
  14. 2017 Medium

    Showed reciprocal and signal-dependent regulation of TTF-1 levels: TTF-1 induces PAX-8 and has anti-tumorigenic effects up to a threshold, and iodinated thyroglobulin tunes TTF-1 via opposing PKA/PKC signaling.

    Evidence Stable transfection with functional/xenograft readouts (PAX-8); follicle model with PKA/PKC agonist-inhibitor dissection (iodinated TG)

    PMID:27573549 PMID:28322461

    Open questions at the time
    • Threshold mechanism for anti-tumorigenic switch unexplained
    • PKC-mediated suppression effector not identified
    • single-lab models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TTF-1's cistrome is selectively reprogrammed across lung adenocarcinoma, SCLC, thyroid, and hypothalamic contexts—and which chromatin or partner inputs dictate target choice—remains unresolved.
  • No unified model linking partner availability to lineage-specific binding
  • physical interaction with ASCL1 not directly demonstrated
  • in vivo coactivator requirements largely untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2
Partners
ASCL1BRN2CBPPARP-1PARP-2PAX8SRC-1TAZ

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 TAZ (transcriptional co-activator with PDZ-binding motif) directly interacts with the NH2-terminal domain of TTF-1 and synergistically activates surfactant protein-C (SP-C) promoter activity in the presence of TTF-1, as demonstrated by mammalian two-hybrid assays and pull-down experiments. Mammalian two-hybrid assay, GST pull-down, deletion analysis, SP-C-luciferase reporter assay The Journal of biological chemistry High 14970209
2001 CBP/p300 and SRC-1 act as coactivators of TTF-1 to regulate surfactant protein-A (SP-A) gene expression. TTF-1 interacts physically with SRC-1 and CBP in vitro; PKA-mediated phosphorylation of TTF-1 facilitates this interaction and leads to TTF-1 acetylation, enhancing its DNA-binding and transcriptional activity on the SP-A promoter. In vitro pull-down, co-immunoprecipitation (SRC-1 immunodepletion), transient transfection/reporter assay, PKA overexpression, adenoviral E1A competition, cAMP treatment with acetylation detection The Journal of biological chemistry High 11713256
2006 PARP-2 (and PARP-1) physically interact with TTF-1: PARP-2 was co-immunoprecipitated with TTF-1 from lung epithelial cell extracts and identified by mass spectrometry; the E domain of PARP-2 binds the C-terminal domain of TTF-1. Both PARP-1 and PARP-2 selectively enhance surfactant protein-B (SP-B/Sftpb) promoter activity in the presence of TTF-1. Co-immunoprecipitation from MLE15 cell extracts, mass spectrometry identification, deletion/domain mapping, Sftpb promoter-luciferase reporter assay The Journal of biological chemistry High 16461352
1995 TTF-1 is required for lung epithelial morphogenesis: antisense oligonucleotide-mediated suppression of TTF-1 translation in embryonic mouse lung explants inhibited branching morphogenesis and caused hyperplastic, disorganized proliferation of airway epithelial cells, while mesenchyme was unaffected. Antisense oligonucleotide inhibition in embryonic mouse lung branching morphogenesis model Developmental biology Medium 8612983
1995 TTF-1 is required for TSH- and IGF-I-stimulated proliferation of thyroid FRTL-5 cells: antisense oligonucleotide blockade of TTF-1 caused ~65% reduction in cell proliferation via the cAMP/PKA pathway. Combined blockade of TTF-1 and Pax-8 did not produce an additive effect. Antisense oligonucleotide treatment, DNA synthesis measurement, cell counting, forskolin stimulation The Journal of biological chemistry Medium 7559458
2004 TTF-1 binds to a site in the RET promoter that overlaps HSCR-associated SNPs, and TTF-1-activated RET transcription is decreased by HSCR-associated alleles. A patient-derived TTF-1 Gly322Ser mutation compromises activation from HSCR-associated RET promoter haplotypes, and TTF-1 and RET are co-expressed in developing human gut. Luciferase reporter assay with RET promoter constructs, mutational analysis, identification of patient TTF-1 mutation, immunohistochemistry for co-expression Human molecular genetics Medium 15548547
2001 Postnatal TTF-1 expression in hypothalamic neurons is developmentally regulated and cell-specific. TTF-1 binds to and transactivates the erbB-2 and LHRH promoters but represses transcription of the preproenkephalin gene, and hypothalamic TTF-1 mRNA increases transiently preceding puberty initiation. In situ hybridization, immunohistochemistry, lesion studies, promoter transactivation assays Molecular and cellular neurosciences Medium 11161473
2006 Conditional deletion of Ttf1 from differentiated neurons in mice caused delayed puberty, reduced reproductive capacity, and shortened reproductive span, associated with reduced hypothalamic expression of pro-reproductive genes, without affecting basal ganglia morphology or function. This places TTF-1 in the transcriptional control of female sexual maturation. Conditional neuron-specific Ttf1 knockout mice (Cre-lox), gene expression profiling of nonhuman primate hypothalamus, behavioral and hormonal phenotyping The Journal of neuroscience High 17182767
2007 A subset of lung adenocarcinoma cell lines expressing TTF-1 exhibit lineage-specific dependency on continued TTF-1 expression: RNAi-mediated TTF-1 knockdown specifically induced growth inhibition and apoptosis only in TTF-1-expressing (TRU lineage) adenocarcinoma lines, not in TTF-1-negative lines. RNA interference knockdown, cell viability assay, apoptosis assay, FISH for gene copy number in patient samples Cancer research Medium 17616654
2011 TTF-1 transcriptionally activates MYBPH (myosin binding protein H), which in turn directly binds ROCK1 (not myosin RLC) to inhibit RLC phosphorylation and LIMK activation, thereby reducing actomyosin organization, decreasing single-cell motility, increasing collective migration, and reducing cancer invasion/metastasis. ChIP and luciferase reporter (TTF-1 → MYBPH), co-immunoprecipitation (MYBPH–ROCK1 interaction), kinase phosphorylation assays, single-cell and collective migration assays, in vivo metastasis models The EMBO journal High 22085929
2009 Three missense mutations in TTF-1/NKX2-1 (L176V, P202L, Q210P) identified in brain-lung-thyroid syndrome patients show loss of transactivation capacity on the human thyroglobulin enhancer/promoter. Importantly, the deficient transcriptional activity of P202L is completely rescued by co-transfected PAX8, whereas L176V and Q210P abolish the PAX8 synergistic effect, demonstrating that TTF-1 and PAX8 cooperate at the thyroglobulin promoter. Transactivation reporter assay, co-transfection with PAX8, patient mutation identification Human molecular genetics Medium 19336474
2013 In small cell lung cancer (SCLC), TTF-1 expression is driven by the neural cell-specific homeoprotein BRN2, which binds to the TTF-1 isoform 2 promoter. BRN2 knockdown markedly reduces TTF-1 expression in SCLC cells; ChIP confirmed BRN2 and FOXA1/2 binding to the TTF-1 promoter. The TTF-1 promoter in SCLC is unmethylated. TTF-1 and BRN2 co-expression is exclusive to SCLC among primary lung tumors. TTF-1 promoter-luciferase reporter assays, expression vector transfection, siRNA knockdown, chromatin immunoprecipitation (ChIP), bisulfite sequencing, immunohistochemistry Laboratory investigation High 23358112
2019 Genome-wide ChIP-seq reveals that TTF-1 binding regions differ by 75% between SCLC (H209) and lung adenocarcinoma (H441) cells; E-box motifs are enriched exclusively in SCLC TTF-1 binding regions. In SCLC, TTF-1 and ASCL1 are co-expressed and bind adjacent sites on target genes to cooperatively regulate neuroendocrine gene transcription. TTF-1 also regulates Bcl-2 family gene expression and exhibits antiapoptotic function in SCLC. ChIP-seq, RNA-seq, co-expression analysis, co-occupancy analysis of TTF-1 and ASCL1 binding sites Molecular oncology High 31782890
2011 TNF-α inhibits TTF-1 protein levels in lung epithelial cells by inhibiting TTF-1 gene transcription; TNF-α suppresses TTF-1 DNA binding to its own promoter and inhibits transcriptional activities of Sp1 and TTF-1 without altering their levels, associated with increased threonine phosphorylation of Sp1. Functional ZBP-89, Sp1/Sp3, and TTF-1 binding sites were identified in the TTF-1 proximal promoter by EMSA, ChIP, and mutational analysis. Deletion analysis of TTF-1 5'-flanking DNA, EMSA, ChIP, mutational analysis, TNF-α treatment, TTF-1 promoter-luciferase reporter assay in H441 and primary alveolar type II cells American journal of physiology. Lung cellular and molecular physiology Medium 21784970
2008 The TTF-1 binding element (TBE) at -171 bp in the hSP-A2 promoter is critical for lung cell-specific, developmental, and hormonal regulation: transgenic mice with TBE mutation showed essentially undetectable fetal lung expression of the hSP-A2 reporter and loss of hormonal (cAMP, IL-1, dexamethasone) regulation, whereas 313-bp wild-type constructs were developmentally regulated and hormonally responsive. Transgenic mouse reporter assay, site-directed mutagenesis of TBE, lung explant culture with hormonal treatments American journal of physiology. Lung cellular and molecular physiology High 18487360
2014 mTOR inhibition promotes TTF-1-dependent redifferentiation of thyroid carcinoma cells: in TTF-1-expressing cell lines, mTOR inhibition upregulates TTF-1 expression and subsequently induces NIS expression and iodine uptake. siRNA knockdown of TTF-1 completely abolishes NIS induction by mTOR inhibition, placing TTF-1 downstream of mTOR and upstream of NIS in this pathway. mTOR inhibitor treatment, siRNA knockdown of TTF-1, mRNA/protein expression analysis, radioactive iodine uptake assay The Journal of clinical endocrinology and metabolism Medium 24712572
2010 TTF-1 transcriptionally activates the α5 nicotinic acetylcholine receptor (nAChR) subunit gene in lung epithelial cells by binding specific TTF-1 response elements in the α5 promoter, as confirmed by site-directed mutagenesis of those elements. Luciferase reporter assay with α5 promoter constructs, exogenous TTF-1 overexpression, site-directed mutagenesis of TTF-1 response elements Respiratory research Medium 21143907
2014 TTF-1, together with FoxA2 and Gata-6, activates transcription from the Claudin-6 (Cldn6) promoter in proximal and distal lung epithelial cell lines; Cldn6 expression in the developing lung co-localizes with TTF-1 and FoxA2 protein. Luciferase reporter assay with 0.5, 1.0, and 2.0-kb Cldn6 promoter constructs, co-transfection with TTF-1/FoxA2/Gata-6 expression vectors, immunofluorescence co-localization Respiratory research Medium 24970044
2005 TTF-1 and PAX8 cooperate synergistically to activate thyroid-specific gene promoters (thyroglobulin, thyroperoxidase, and NIS regulatory regions) in hepatoma cells; low transcriptional activation occurs with either factor alone, but strong activation requires both together. This functional protein-protein cooperation was imaged in vivo in nude mice. Luciferase reporter assay with thyroid-specific promoter/enhancer constructs, stable transfection of hepatoma cells, in vivo bioluminescence imaging Journal of nuclear medicine Medium 15872358
1998 Overexpression of TTF-1 together with PAX-8 restores thyroglobulin (Tg) gene promoter activity in TTF-1/PAX-8-deficient thyroid carcinoma cell lines (ARO, WRO); neither factor alone is sufficient, and activity is restricted to thyroid-lineage cells. Tg promoter-β-galactosidase reporter co-transfection with TTF-1 and PAX-8 expression vectors, RT-PCR Surgery Medium 9854590
2017 In thyroid carcinoma cell lines, stable transfection of TTF-1 reciprocally induces PAX-8 expression. Induction of TTF-1 affects cell proliferation, migration, and tumorigenicity more than PAX-8, with anti-proliferative and anti-tumorigenic effects observed up to a threshold expression level. Stable transfection with TTF-1 and PAX-8 expression vectors, cell growth assay, cell cycle analysis, migration assay, in vivo tumorigenicity (xenograft) International journal of oncology Medium 27573549
1994 TTF-1 and PAX-8 activate transcription from thyroglobulin and thyroperoxidase (TPO) promoters in thyroid follicular cells. TTF-1 mRNA is consistently detectable in papillary thyroid carcinomas but absent in anaplastic carcinomas, suggesting TTF-1 expression is linked to the differentiated thyroid phenotype. Expression of TTF-1 and PAX-8 alone is not sufficient to drive the differentiated thyroid phenotype. mRNA quantification (Northern/RT-PCR), immunohistochemistry, functional promoter assays referenced as prior work Cancer research Low 8062273
2017 Iodinated thyroglobulin regulates TTF-1 (and PAX8) expression in thyroid follicular cells through TSH/TSHR-mediated signaling: lowly iodinated TG activates cAMP-PKA to upregulate TTF-1, while highly iodinated TG activates PLC-PKC to suppress TTF-1. Blocking PKC pathway reverses highly-iodinated TG-mediated TTF-1 suppression. In vitro thyroid follicle model, PKA/PKC agonist and inhibitor treatments, protein/mRNA expression analysis Journal of cellular biochemistry Medium 28322461

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 TTF-1 expression in pulmonary adenocarcinomas. The American journal of surgical pathology 296 12023581
1994 Expression of thyroid-specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasms. Cancer research 222 8062273
2007 Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1. Cancer research 173 17616654
2009 Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Human molecular genetics 151 19336474
2004 TAZ interacts with TTF-1 and regulates expression of surfactant protein-C. The Journal of biological chemistry 151 14970209
1995 TTF-1 regulates lung epithelial morphogenesis. Developmental biology 145 8612983
2012 Mesonephric adenocarcinomas of the uterine cervix and corpus: HPV-negative neoplasms that are commonly PAX8, CA125, and HMGA2 positive and that may be immunoreactive with TTF1 and hepatocyte nuclear factor 1-β. The American journal of surgical pathology 134 22456609
2003 p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. American journal of clinical pathology 122 12760288
2017 SMARCA4-deficient pulmonary adenocarcinoma: clinicopathological, immunohistochemical, and molecular characteristics of a novel aggressive neoplasm with a consistent TTF1neg/CK7pos/HepPar-1pos immunophenotype. Virchows Archiv : an international journal of pathology 117 28555282
2010 An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63. The American journal of surgical pathology 98 20182342
2001 TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion. Molecular and cellular neurosciences 98 11161473
2004 Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade. Histopathology 94 15279630
2000 Is TTF1 a good immunohistochemical marker to distinguish primary from metastatic lung adenocarcinomas? Pathology, research and practice 88 11156325
2009 TTF-1 expression in ovarian and uterine epithelial neoplasia and its potential significance, an immunohistochemical assessment with multiple monoclonal antibodies and different secondary detection systems. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 83 19047914
2011 MYBPH, a transcriptional target of TTF-1, inhibits ROCK1, and reduces cell motility and metastasis. The EMBO journal 75 22085929
2004 TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease. Human molecular genetics 74 15548547
2006 TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 72 16680154
2001 Role of CBP/p300 and SRC-1 in transcriptional regulation of the pulmonary surfactant protein-A (SP-A) gene by thyroid transcription factor-1 (TTF-1). The Journal of biological chemistry 67 11713256
2013 A mutation in TTF1/NKX2.1 is associated with familial neuroendocrine cell hyperplasia of infancy. Chest 65 23787483
2009 TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival. The Journal of pathology 61 18932182
2015 An Integrated Molecular Analysis of Lung Adenocarcinomas Identifies Potential Therapeutic Targets among TTF1-Negative Tumors, Including DNA Repair Proteins and Nrf2. Clinical cancer research : an official journal of the American Association for Cancer Research 57 25878335
2014 The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non-small cell lung cancer. Human pathology 55 24746197
2010 TTF1 expression in normal lung neuroendocrine cells and related tumors: immunohistochemical study comparing two different monoclonal antibodies. Virchows Archiv : an international journal of pathology 54 20694477
2006 PARP-2 interacts with TTF-1 and regulates expression of surfactant protein-B. The Journal of biological chemistry 49 16461352
2006 Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 17182767
1995 Function of the homeo and paired domain proteins TTF-1 and Pax-8 in thyroid cell proliferation. The Journal of biological chemistry 47 7559458
2014 The relationship between TTF-1 expression and EGFR mutations in lung adenocarcinomas. PloS one 45 24743427
2009 Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer. Proceedings of the National Academy of Sciences of the United States of America 45 19279207
2004 CD117, CK20, TTF-1, and DNA topoisomerase II-alpha antigen expression in small cell tumors. Journal of cutaneous pathology 45 14984578
2019 SOX10, GATA3, GCDFP15, Androgen Receptor, and Mammaglobin for the Differential Diagnosis Between Triple-negative Breast Cancer and TTF1-negative Lung Adenocarcinoma. The American journal of surgical pathology 43 30628926
2013 Update on hypophysitis and TTF-1 expressing sellar region masses. Brain pathology (Zurich, Switzerland) 43 23701182
2007 Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis. Histopathology 43 17727473
2007 WT1, monoclonal CEA, TTF1, and CA125 antibodies in the differential diagnosis of lung, breast, and ovarian adenocarcinomas in serous effusions. Diagnostic cytopathology 39 17497661
2008 Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells. British journal of cancer 38 18682709
2014 mTOR Inhibition promotes TTF1-dependent redifferentiation and restores iodine uptake in thyroid carcinoma cell lines. The Journal of clinical endocrinology and metabolism 37 24712572
2015 Distinct Characteristics of Small Cell Lung Cancer Correlate With Central or Peripheral Origin: Subtyping Based on Location and Expression of Transcription Factor TTF-1. Medicine 35 26705222
2009 Small cell lung cancer: significance of RB alterations and TTF-1 expression in its carcinogenesis, phenotype, and biology. Endocrine pathology 34 19390995
2013 An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: III. Expressions of EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63 in normal mucosa and in 42 cases. International journal of clinical and experimental pathology 33 23573309
2016 Induction of TTF-1 or PAX-8 expression on proliferation and tumorigenicity in thyroid carcinomas. International journal of oncology 30 27573549
2019 Comparative analysis of TTF-1 binding DNA regions in small-cell lung cancer and non-small-cell lung cancer. Molecular oncology 27 31782890
2013 Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer. Laboratory investigation; a journal of technical methods and pathology 27 23358112
2017 TTF-1- and/or CD56-positive Circulating Tumor Cells in patients with small cell lung cancer (SCLC). Scientific reports 26 28349943
2012 Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma. Virchows Archiv : an international journal of pathology 26 23064619
2014 Developmental lung expression and transcriptional regulation of claudin-6 by TTF-1, Gata-6, and FoxA2. Respiratory research 25 24970044
2013 TTF-1 expression in breast carcinoma: an unusual but real phenomenon. Histopathology 25 24111789
2023 Thyroid transcription factor-1 (TTF-1) expression and the efficacy of combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapy in non-squamous non-small cell lung cancer. Translational lung cancer research 23 37854151
2019 Value of SATB2, ISL1, and TTF1 to differentiate rectal from other gastrointestinal and lung well-differentiated neuroendocrine tumors. Pathology, research and practice 23 31133441
2017 Pituicytoma: Review of commonalities and distinguishing features among TTF-1 positive tumors of the central nervous system. Annals of diagnostic pathology 23 28807344
1998 Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines. Surgery 23 9854590
2015 The expression of TTF-1 and Napsin A in early-stage lung adenocarcinoma correlates with the results of surgical treatment. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 25982999
2008 Immunohistochemical expression of TTF-1 in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity. Pathology international 22 18067638
2022 Association of thyroid transcription factor-1 (TTF-1) expression with efficacy of PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in advanced non-squamous non-small cell lung cancer. Translational lung cancer research 20 36519019
2018 Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens. Human pathology 20 30385371
2016 Utility of TTF-1 and Napsin-A in the work-up of malignant effusions. Diagnostic cytopathology 20 26799356
2011 Thyroid transcription factor-1 (TTF-1) gene: identification of ZBP-89, Sp1, and TTF-1 sites in the promoter and regulation by TNF-α in lung epithelial cells. American journal of physiology. Lung cellular and molecular physiology 20 21784970
2009 TTF-1 expression in nephroblastoma. The American journal of surgical pathology 20 19011567
2022 Non-small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours. Histopathology 19 36130728
2014 Analysis of clinical characteristics and differential diagnosis of the lung biopsy specimens in 99 adenocarcinoma cases and 111 squamous cell carcinoma cases: utility of an immunohistochemical panel containing CK5/6, CK34βE12, p63, CK7 and TTF-1. Pathology, research and practice 19 25063315
2023 TTF-1 Expression and Clinical Outcomes of Combined Chemoimmunotherapy in Patients With Advanced Lung Adenocarcinoma: A Prospective Observational Study. JTO clinical and research reports 18 37020925
2018 The expression of TTF1, CDX2 and ISL1 in 74 poorly differentiated neuroendocrine carcinomas. Annals of diagnostic pathology 18 30236546
2016 TTF-1 and PAX5 Are Frequently Expressed in Combined Merkel Cell Carcinoma. The American Journal of dermatopathology 17 27322785
2008 EGFR, TTF-1 and Mdm2 expression in stage III non-small cell lung cancer: a positive association. Lung cancer (Amsterdam, Netherlands) 17 18355939
2008 TTF-1 response element is critical for temporal and spatial regulation and necessary for hormonal regulation of human surfactant protein-A2 promoter activity. American journal of physiology. Lung cellular and molecular physiology 17 18487360
2005 Effects of Pax8 and TTF-1 thyroid transcription factor gene transfer in hepatoma cells: imaging of functional protein-protein interaction and iodide uptake. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 17 15872358
2021 Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations. JTO clinical and research reports 16 34746884
2020 TTF-1 Positive Primary Small Cell Carcinoma of the Breast: A Case Report and Review of the Literature. Frontiers in endocrinology 16 32411090
2013 EGFR and TTF-1 gene amplification in surgically resected lung adenocarcinomas: clinicopathologic significance and effect on response to EGFR-tyrosine kinase inhibitors in recurred cases. Annals of surgical oncology 16 23525704
2021 NKX2.1 (TTF1) germline mutation associated with pulmonary fibrosis and lung cancer. ERJ open research 15 34760996
2019 When tumor doesn't read textbook. Third case of TTF1 and p40 co-expression in the same tumour cells in a non-small cell carcinoma. A potential new entity to consider? Pathologica 15 31388196
2018 Positivity for GATA3 and TTF-1 (SPT24), and Negativity for Monoclonal PAX8 Expand the Biomarker Profile of the Solid Cell Nests of the Thyroid Gland. Endocrine pathology 15 29313264
2018 Immunohistochemical analysis and comparison of napsin A, TTF1, SPA and CK7 expression in primary lung adenocarcinoma. Biotechnic & histochemistry : official publication of the Biological Stain Commission 15 29956575
2024 TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities. Virchows Archiv : an international journal of pathology 14 39377914
2016 Expression of Tenascin C, EGFR, E-Cadherin, and TTF-1 in Medullary Thyroid Carcinoma and the Correlation with RET Mutation Status. International journal of molecular sciences 14 27409604
2016 RETRACTED: TTF1, in the Form of Nanoparticles, Inhibits Angiogenesis, Cell Migration and Cell Invasion In Vitro and In Vivo in Human Hepatoma through STAT3 Regulation. Molecules (Basel, Switzerland) 14 27834930
2015 Co-expression of TTF-1 and neuroendocrine markers in the human fetal lung and pulmonary neuroendocrine tumors. Acta histochemica 14 25722034
2005 Aberrant expression of TTF-1 and forkhead factor HFH-4 in atrophic gastritis and ciliated metaplasia suggests gastric broncho-pulmonary transdetermination. The Journal of pathology 14 15912575
2021 SMARCA4 (BRG1) and SMARCB1 (INI1) expression in TTF-1 negative neuroendocrine carcinomas including merkel cell carcinoma. Pathology, research and practice 13 33581550
2016 TTF1-NPs Induce ERS-Mediated Apoptosis and Inhibit Human Hepatoma Cell Growth In Vitro and In Vivo. Oncology research 13 27131317
2012 IMP3, NESP55, TTF-1 and CDX2 serve as an immunohistochemical panel in the distinction among small-cell carcinoma, gastrointestinal carcinoid, and pancreatic endocrine tumor metastasized to the liver. Applied immunohistochemistry & molecular morphology : AIMM 13 22495359
2010 TTF-1 regulates α5 nicotinic acetylcholine receptor (nAChR) subunits in proximal and distal lung epithelium. Respiratory research 13 21143907
2021 An algorithmic approach utilizing CK7, TTF1, beta-catenin, CDX2, and SSTR2A can help differentiate between gastrointestinal and pulmonary neuroendocrine carcinomas. Virchows Archiv : an international journal of pathology 12 33733343
2020 The Incidence of Labelling of Non-Lung Adenocarcinomas With Antibodies Against TTF-1 and Diagnostic Implications. Applied immunohistochemistry & molecular morphology : AIMM 12 31135446
2017 Expressions and significances of TTF-1 and PTEN in early endometrial cancer. European review for medical and pharmacological sciences 12 28745797
2011 Inhibition of tumor angiogenesis by TTF1 from extract of herbal medicine. World journal of gastroenterology 12 22171128
2021 Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non-small cell lung carcinoma. Journal of pathology and translational medicine 11 34233113
2020 CDX2, SATB2, GATA3, TTF1, and PAX8 Immunohistochemistry in Krukenberg Tumors. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 11 32045390
2018 Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-Associated Hepatocellular Carcinomas. Asian Pacific journal of cancer prevention : APJCP 11 29373917
2017 Correlation between molecular analysis, diagnosis according to the 2015 WHO classification of unresected lung tumours and TTF1 expression in small biopsies and cytology specimens from 344 non-small cell lung carcinoma patients. Pathology 11 28811082
2011 TTF1-induced apoptosis of HepG-2 cells through a mitochondrial pathway. Oncology reports 11 21637920
2008 The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the diagnosis of primary and secondary lung carcinomas. Saudi medical journal 11 18626520
2021 Differential Expression of PD-L1 in Central and Peripheral and TTF1-Positive and -Negative Small-Cell Lung Cancer. Frontiers in medicine 10 33585516
2019 REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression. Journal of cancer research and clinical oncology 10 31428934
2018 Differential expression of neuroendocrine markers, TTF-1, p53, and Ki-67 in cervical and pulmonary small cell carcinoma. Medicine 10 30045295
2018 TTF1 Expression in Pulmonary Metastatic Rectal Adenocarcinoma. Case reports in gastrointestinal medicine 10 30631609
2015 Replication and Meta-Analysis of Common Gene Mutations in TTF1 and TTF2 with Papillary Thyroid Cancer. Medicine 10 26356687
2023 SOX11 Is an Effective Discriminatory Marker, When Used in Conjunction With CK20 and TTF1, for Merkel Cell Carcinoma: Comparative Analysis of SOX11, CK20, PAX5, and TTF1 Expression in Merkel Cell Carcinoma and Pulmonary Small Cell Carcinoma. Archives of pathology & laboratory medicine 9 36745184
2017 Iodinated TG in Thyroid Follicular Lumen Regulates TTF-1 and PAX8 Expression via TSH/TSHR Signaling Pathway. Journal of cellular biochemistry 9 28322461
2024 Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features. Virchows Archiv : an international journal of pathology 8 38710944
2020 Aberrant TTF-1 Expression in Peripheral T-Cell Lymphomas: A Diagnostic Pitfall. International journal of surgical pathology 8 32772757
2018 TTF1‑NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR pathway and activating JNK in human liver cancer cells. Oncology reports 8 29328481

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