ArticleOncogene2021
Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Interaction of NDRG1 and TGM2 Modulates DNA Replication and Repair.Molecular cancer research : MCR · 2026Article
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Identification and validation of an 11-kinase signature that predicts chemo- and radiosensitivity in gastric cancer.EBioMedicine · 2026Article
- SPECT as a translational non-invasive method to assess occupancy of the tissue transglutaminase-2 by zampilimab in the mouse lung.Respiratory research · 2026Article
- Impact of treatment history on drug resistance of metastatic colorectal cancer organoids.iScience · 2025Article
- Multi-omic analyses reveal aberrant DNA methylation patterns and the associated biomarkers of nasopharyngeal carcinoma and its cancer stem cells.Scientific reports · 2025Article
- Continuous map of early hematopoietic stem cell differentiation across human lifetime.Nature communications · 2025Article
- TMT-Based Quantitative Proteomic Profiling of Human Esophageal Cancer Cells Reveals the Potential Mechanism and Potential Therapeutic Targets Associated With Radioresistance.Proteomics. Clinical applications · 2025Article
- Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma.Antioxidants (Basel, Switzerland) · 2024Article
- Transglutaminase 2-mediated histone monoaminylation and its role in cancer.Bioscience reports · 2024Review
- Identifying polyamine related biomarkers in diagnosis and treatment of ulcerative colitis by integrating bulk and single-cell sequencing data.Scientific reports · 2024Article
- COL5A1 promotes triple-negative breast cancer progression by activating tumor cell-macrophage crosstalk.Oncogene · 2024Article
- Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis.World journal of gastrointestinal oncology · 2024Article
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
- Mutant p53 gains oncogenic functions through a chromosomal instability-induced cytosolic DNA response.Nature communications · 2024Article
- Transglutaminase 2 in diabetes mellitus: Unraveling its multifaceted role and therapeutic implications for vascular complications.Theranostics · 2024Review
- The upregulation of TGM2 is associated with poor prognosis and the shaping of the inflammatory tumor microenvironment in lung squamous cell carcinoma.American journal of cancer research · 2024Article
- CRISPR/Cas9: a powerful tool in colorectal cancer research.Journal of experimental & clinical cancer research : CR · 2023Review
- Transglutaminase 2 is associated with adverse colorectal cancer survival and represents a therapeutic target.Cancer gene therapy · 2023Article
- TIP60 is required for tumorigenesis in non-small cell lung cancer.Cancer science · 2023Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite a high clinical need for the treatment of colorectal carcinoma (CRC) as the second leading cause of cancer-related deaths, targeted therapies are still limited. The multifunctional enzyme Transglutaminase 2 (TGM2), which harbors transamidation and GTPase activity, has been implicated in the development and progression of different types of human cancers. However, the mechanism and role of TGM2 in colorectal cancer are poorly understood. Here, we present TGM2 as a promising drug target.In primary patient material of CRC patients, we detected an increased expression and enzymatic activity of TGM2 in colon cancer tissue in comparison to matched normal colon mucosa cells. The genetic ablation of TGM2 in CRC cell lines using shRNAs or CRISPR/Cas9 inhibited cell expansion and tumorsphere formation. In vivo, tumor initiation and growth were reduced upon genetic knockdown of TGM2 in xenotransplantations. TGM2 ablation led to the induction of Caspase-3-driven apoptosis in CRC cells. Functional rescue experiments with TGM2 variants revealed that the transamidation activity is critical for the pro-survival function of TGM2. Transcriptomic and protein-protein interaction analyses applying various methods including super-resolution and time-lapse microscopy showed that TGM2 directly binds to the tumor suppressor p53, leading to its inactivation and escape of apoptosis induction.We demonstrate here that TGM2 is an essential survival factor in CRC, highlighting the therapeutic potential of TGM2 inhibitors in CRC patients with high TGM2 expression. The inactivation of p53 by TGM2 binding indicates a general anti-apoptotic function, which may be relevant in cancers beyond CRC.
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