Observational studyNeoplasia (New York, N.Y.)2013
Extracellular tissue transglutaminase activates noncanonical NF-κB signaling and promotes metastasis in ovarian cancer.
Observational study in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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.
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Who cites it
43 citing papers in PubMed, 55 citations in OpenAlex.
- Platelet-Prostate cancer crosstalk driving disparities and therapeutic vulnerabilities.Discover oncology · 2026Review
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Novel PROTACs targeting tissue transglutaminase (TG2) suppress tumorigenicity of ovarian cancer cells.European journal of medicinal chemistry · 2026Article
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
- Cell-Impermeable Inhibitors Confirm That Intracellular Human Transglutaminase 2 Is Responsible for the Transglutaminase-Associated Cancer Phenotype.International journal of molecular sciences · 2023Article
- Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines.Cell death & disease · 2023Article
- Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme.Cellular and molecular life sciences : CMLS · 2023Review
- Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Review
- Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop.Molecular cancer · 2022Article
- Multi-Omics Analysis of Glioblastoma and Glioblastoma Cell Line: Molecular Insights Into the Functional Role of GPR56 and TG2 in Mesenchymal Transition.Frontiers in oncology · 2022Article
- Exploring the Role of Transglutaminase in Patients with Glioblastoma: Current Perspectives.OncoTargets and therapy · 2022Review
- Role of Tissue Transglutaminase Catalytic and Guanosine Triphosphate-Binding Domains in Renal Cell Carcinoma Progression.ACS omega · 2020Article
- Expression of p52, a non-canonical NF-kappaB transcription factor, is associated with poor ovarian cancer prognosis.Biomarker research · 2020Article
- NF-κB Signaling in Ovarian Cancer.Cancers · 2019Review
- Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target.Molecular carcinogenesis · 2019Article
- Small Molecules Target the Interaction between Tissue Transglutaminase and Fibronectin.Molecular cancer therapeutics · 2019Article
- Transglutaminase 2: The Maestro of the Oncogenic Mediators in Renal Cell Carcinoma.Medical sciences (Basel, Switzerland) · 2019Review
- The Role of Tissue Transglutaminase in Cancer Cell Initiation, Survival and Progression.Medical sciences (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue transglutaminase (TG2) is a multifunctional protein that binds to fibronectin and exerts protein transamidating activity in the presence of Ca(2+). We previously reported that TG2 is upregulated in ovarian tumors and enhances intraperitoneal (i.p.) metastasis. TG2 is secreted abundantly in ovarian cancer (OC) ascites as an active enzyme, yet its function in the extracellular compartment remains unknown. To study the distinct functions of secreted TG2, we used recombinant His6-tagged TG2 and catalytically inactive enzyme in vitro and in vivo. By using i.p. and orthotopic ovarian xenografts, we show that extracellular transglutaminase promoted OC peritoneal metastasis. The main pathway activated by extracellular TG2 was noncanonical nuclear factor-kappa B (NF-κB) signaling, and the enzymatic function of the protein was required to induce phosphorylation of IκB kinase α and processing of the precursor protein p100 into the active p52 subunit. A specific target of TG2-activated p52/RelB complex is the hyaluronan receptor, CD44. Noncanonical NF-κB activation by extracellular TG2 induced CD44 up-regulation and epithelial-to-mesenchymal transition, contributing to increased cancer cell invasiveness and OC peritoneal dissemination. Taken together, our data support that noncanonical NF-κB activation is the pathway through which extracellular TG2 promotes OC metastasis.
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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.