ArticleOncogene2010
Transglutaminase 2 suppresses apoptosis by modulating caspase 3 and NF-kappaB activity in hypoxic tumor cells.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 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.
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Who cites it
76 citing papers in PubMed, 126 citations in OpenAlex.
- Inhibition of TGM2 enhances cisplatin sensitivity in MSH2-deficient bladder cancer.Cell death discovery · 2026Article
- Removal or inhibition of transglutaminase 2 decreases cellular stress, supporting tissue preservation, and recovery after SCI.Acta neuropathologica communications · 2025Article
- Transglutaminase 2 Regulates HSF1 Gene Expression in the Acute Phase of Fish Optic Nerve Regeneration.International journal of molecular sciences · 2024Article
- Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors.Cells · 2024Review
- Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Transglutaminase 2 in breast cancer metastasis and drug resistance.Frontiers in cell and developmental biology · 2024Review
- Lung-specific interleukin 6 mediated transglutaminase 2 activation and cardiopulmonary fibrogenesis.Frontiers in immunology · 2024Article
- Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines.Cell death & disease · 2023Article
- Transglutaminase 2 Prevents Premature Senescence and Promotes Osteoblastic Differentiation of Mesenchymal Stem Cells through NRF2 Activation.Stem cells international · 2023Article
- Article
- Hypoxia-mediated stabilization of HIF1A in prostatic intraepithelial neoplasia promotes cell plasticity and malignant progression.Science advances · 2022Article
- Double-Stranded RNA Enhances Matrix Metalloproteinase-1 and -13 Expressions through TLR3-Dependent Activation of Transglutaminase 2 in Dermal Fibroblasts.International journal of molecular sciences · 2022Article
- Erythrocyte transglutaminase-2 combats hypoxia and chronic kidney disease by promoting oxygen delivery and carnitine homeostasis.Cell metabolism · 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
- miR‑125a‑5p reverses epithelial‑mesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer.Molecular medicine reports · 2021Article
- Review
- The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2.International journal of molecular sciences · 2021Review
- The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment.Cancers · 2021Review
- Transglutaminase 2 mediates transcriptional regulation through BAF250a polyamination.Genes & genomics · 2021Article
- Downregulated PEG3 ameliorates cardiac fibrosis and myocardial injury in mice with ischemia/reperfusion through the NF-κB signaling pathway.Journal of bioenergetics and biomembranes · 2020Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of hypoxia-inducible factor-1 (HIF-1) correlates with poor clinical outcomes and confers resistance to the apoptosis of the tumor cells that are exposed to hypoxia. Presently, the mechanism underlying this phenomenon is poorly understood. In this study we provide evidence that transglutaminase 2 (TG2), an enzyme that catalyses protein crosslinking reactions, is a transcriptional target of HIF-1 to enhance the survival of hypoxic cells. We found that hypoxia induces TG2 expression through an HIF-1 dependent pathway and concurrently activates intracellular TG2. The hypoxic cells overexpressing TG2 showed resistance to apoptosis. Conversely, the hypoxic cells treated with either TG2 inhibitor or small interfering RNA (siRNA) became sensitive to apoptosis. Activation of TG2 in response to hypoxic stress inhibited caspase-3 activity by forming crosslinked multimer, resulting in insoluble aggregates. TG2 also activates nuclear factor (NF)-kappaB pathway after hypoxic stress, and thereby induces the expression of cellular inhibitor of apoptosis 2. The anti-apoptotic role of TG2 was further confirmed in vivo using xenografts in athymic mice. Our results indicate that TG2 is an anti-apoptotic mediator of HIF-1 through modulating both apoptosis and survival pathways and may confer a selective growth advantage to tumor cells. These findings suggest that the inhibition of TG2 may offer a novel strategy for anticancer therapy.
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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.