ArticleThe Journal of biological chemistry2009
Tissue transglutaminase regulates matrix metalloproteinase-2 in ovarian cancer by modulating cAMP-response element-binding protein activity.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Novel PROTACs targeting tissue transglutaminase (TG2) suppress tumorigenicity of ovarian cancer cells.European journal of medicinal chemistry · 2026Article
- Discovery and Characterization of PROTACs Targeting Tissue Transglutaminase (TG2).Journal of medicinal chemistry · 2023Article
- Molecular Basis of Transglutaminase-2 and Muscarinic Cholinergic Receptors in Experimental Myopia: A Target for Myopia Treatment.Biomolecules · 2023Article
- Review
- Quantitative biophysical metrics for rapid evaluation of ovarian cancer metastatic potential.Molecular biology of the cell · 2022Article
- Vocal Fold Fibroblasts in Reinke's Edema Show Alterations Involved in Extracellular Matrix Production, Cytokine Response and Cell Cycle Control.Biomedicines · 2021Article
- The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment.Cancers · 2021Review
- Abiraterone Acetate Induces CREB1 Phosphorylation and Enhances the Function of the CBP-p300 Complex, Leading to Resistance in Prostate Cancer Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020Review
- Small Molecules Target the Interaction between Tissue Transglutaminase and Fibronectin.Molecular cancer therapeutics · 2019Article
- Review
- Transglutaminase 2: Friend or foe? The discordant role in neurons and astrocytes.Journal of neuroscience research · 2018Review
- Article
- Tissue transglutaminase-interleukin-6 axis facilitates peritoneal tumor spreading and metastasis of human ovarian cancer cells.Laboratory animal research · 2015Article
- Transglutaminase is a tumor cell and cancer stem cell survival factor.Molecular carcinogenesis · 2015Review
- Transglutaminase Is Required for Epidermal Squamous Cell Carcinoma Stem Cell Survival.Molecular cancer research : MCR · 2015Article
- Article
- EMT-Inducing Molecular Factors in Gynecological Cancers.BioMed research international · 2015Review
- Transglutaminase 2 in cancer.American journal of cancer research · 2015Article
- Lack of transglutaminase 2 diminished T-cell responses in mice.Immunology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue transglutaminase 2 (TG2) is overexpressed in epithelial ovarian cancer (EOC) and promotes intraperitoneal metastasis. How TG2 facilitates the spread of EOC is unknown. Here, we show that TG2 regulates the expression and function of matrix metalloproteinase-2 (MMP-2), a critical mediator of tissue invasiveness. TG2 knockdown down-regulates MMP-2 protein and mRNA expression in SKOV3, IGROV-1, MDA-MB-436, and PC-3 cancer cells. TG2 knockdown or inhibition of TG2 activity using KCC009 decreases MMP-2 gelatinase activity in cancer cells. MMP-2 expression and function are regulated by TG2 at transcriptional level, as demonstrated by quantitative PCR and reporter assays. We used bioinformatics and chromatin immunoprecipitation to identify a CREB binding site in the MMP-2 promoter. Binding of CREB to the MMP-2 promoter was diminished in cells that expressed decreased TG2 levels. TG2 knockdown decreased CREB phosphorylation, and CREB knockdown decreased MMP-2 expression. The effect of TG2 on CREB activity and MMP-2 transcription is mediated by TG2-dependent degradation of protein phosphatase 2 (PP2A-alpha). We show that PP2A-alpha complexes with and is targeted for degradation by TG2. In addition to their related in vitro expression levels, TG2 and MMP-2 expression were significantly correlated in vivo, as shown by concordant immunostaining in peritoneal xenografts and in human ovarian tumors. The capacity of TG2 to regulate MMP-2 expression in vitro and in vivo identifies a mechanism that may facilitate tissue invasion and the spread of EOC. The demonstration that TG2 induced degradation of PP2A-alpha activates CREB, and thereby increases MMP-2 transcription, provides novel mechanistic insight into the pro- metastatic function of TG2.
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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.