ArticleOncogenesis2015
TIFA, an inflammatory signaling adaptor, is tumor suppressive for liver cancer.
Article in Oncogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- TIFA: a signaling hub linking inflammation, innate immunity, and human disease.Frontiers in immunology · 2026Review
- Staphylococcal Enterotoxin A Shapes Monocyte Transcription and Macrophage Polarization: Implications for Immune Responses in Infection and Inflammation.European journal of immunology · 2025Article
- Cytokines reprogram airway sensory neurons in asthma.bioRxiv : the preprint server for biology · 2024Article
- TIFA contributes to periodontitis in diabetic mice via activating the NF‑κB signaling pathway.Molecular medicine reports · 2024Article
- Article
- The Role of TLR4 in the Immunotherapy of Hepatocellular Carcinoma: Can We Teach an Old Dog New Tricks?Cancers · 2023Review
- TIFA promotes colorectal cancer cell proliferation in an RSK- and PRAS40-dependent manner.Cancer science · 2022Article
- Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth.Bioengineered · 2021Article
- CCL16 maintains stem cell-like properties in breast cancer by activating CCR2/GSK3β/β-catenin/OCT4 axis.Theranostics · 2021Article
- Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner.Stem cell research & therapy · 2020Article
- PPA1 promotes NSCLC progression via a JNK- and TP53-dependent manner.Oncogenesis · 2019Article
- The potential probiotic Lactobacillus rhamnosus CNCM I-3690 strain protects the intestinal barrier by stimulating both mucus production and cytoprotective response.Scientific reports · 2019Article
- Low dosage of arsenic trioxide (AsJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
- ICAM3 mediates inflammatory signaling to promote cancer cell stemness.Cancer letters · 2018Article
- TBX21 predicts prognosis of patients and drives cancer stem cell maintenance via the TBX21-IL-4 pathway in lung adenocarcinoma.Stem cell research & therapy · 2018Article
- Novel hybrid molecule overcomes the limited response of solid tumours to HDAC inhibitors via suppressing JAK1-STAT3-BCL2 signalling.Theranostics · 2018Article
- Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones.Scientific reports · 2017Article
- Inactivation of p38 MAPK contributes to stem cell-like properties of non-small cell lung cancer.Oncotarget · 2017Article
- RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome.Biochimica et biophysica acta · 2016Article
- TIFA suppresses hepatocellular carcinoma progression via MALT1-dependent and -independent signaling pathways.Signal transduction and targeted therapyArticle
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
TIFA (TNF receptor associated factor (TRAF)-interacting protein with a Forkhead-associated (FHA) domain), also called T2BP, was first identified using a yeast two-hybrid screening. TIFA contains a FHA domain, which directly binds phosphothreonine and phosphoserine, and a consensus TRAF6-binding motif. TIFA-mediated oligomerization and poly-ubiquitinylation of TRAF6 mediates signaling downstream of the Tumor necrosis factor alpha receptor 1 (TNFaR-I) and interleukin-1/Toll-like receptor 4 (TLR4) pathways. Examining TIFA expression in hepatocellular carcinoma (HCC) tissues microarrays, we noted marked decreases TIFA reactivity in tumor versus control samples. In agreement, we found that HCC cell lines show reduced TIFA expression levels versus normal liver controls. Reconstituting TIFA expression in HCC cell lines promoted two independent apoptosis signaling pathways: the induction of p53 and cell cycle arrest, and the activation of caspase-8 and caspase-3. In contrast, the expression of a non-oligomerizing mutant of TIFA impacted cells minimally, and suppression of TIFA expression protected cells from apoptosis. Mice bearing TIFA overexpression hepatocellular xenografts develop smaller tumors versus TIFA mutant tumors; terminal deoxynucleotidyl transferase dUTP nick end labeling staining demonstrates increased cell apoptosis, and decreased proliferation, reflecting cell cycle arrest. Interestingly, p53 has a greater role in decreased proliferation than cell death, as it appeared dispensable for TIFA-induced cell killing. The findings demonstrate a novel suppressive role of TIFA in HCC progression via promotion of cell death independent of p53.
Identifiers
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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.