TGM2 (Transglutaminase 2)

Our study further identified a putative NDRG1-TGM2 binding site and show that the physical interaction between NDRG1 and TGM2 is required for efficient DNA replication. Implications: This study reveals a previously unrecognized nuclear function for NDRG1 and TGM2 in regulating DNA replication fork stability and recovery and uncovers a stress-responsive mechanism that supports replication homeostasis in cancer cells and advance our understanding of how extracellular signals are integrated with replication and repair pathways.

This molecular axis is particularly significant for its role in the maintenance of epidermal cancer stem (ECS) cells, which contribute to tumor progression and therapy resistance. While the definitive link between the TG2-GPR56 complex and systemic metastasis in cSCC is currently being elucidated, significant evidence from analogous malignancies and in vitro keratinocyte models provides a clear mechanistic roadmap for its involvement in tumor invasion.

Collectively, crocetin could suppress CRC progression by targeting TGM2/JAK2/STAT3 signaling pathway, supporting its potential as a therapeutic agent for CRC.

To explore therapeutic implications, transcriptomics-guided drug repositioning combined with molecular docking analysis identified five candidate compounds-celastrol, fedratinib, pevonedistat, tozasertib, and withaferin A-predicted to target key network hubs. Overall, this in silico study provides a ceRNA-centered regulatory framework for GC and prioritizes biologically informed biomarkers and repositioned drug candidates with potential applicability across other malignancies to converge precision oncology.

Direct analysis of undiluted clinical plasma samples from healthy individuals and liver cancer patients showed that TGM2 concentrations measured using the proposed LFA were consistent with those obtained by a commercial enzyme-linked immunosorbent assay. These results support the applicability of the nanozyme-amplified LFA as a proof-of-concept platform for clinically relevant TGM2 detection.

Clinically, high endothelial TGM2 and H3Q5Ser levels predict poorer prognosis. Collectively, the TGM2-serotonylation axis in endothelial cells represents a promising therapeutic target to disrupt tumor angiogenesis and CRC progression, with potential to synergize with immunotherapy by normalizing tumor vasculature and enhancing anti-tumor immunity.

Collectively, these findings identify ALDH2 as a key tumor suppressor in HNSC, including OSCC, and highlight the therapeutic potential of activating ALDH2, NR4A1, and TGM2. Moreover, stabilization of the ALDH2-ALDH6A1 complex may offer a viable strategy for disease prevention and treatment, even in the context of frequent ALDH2 mutations.

This integrated framework successfully identified has-miR-6756-5p as both a diagnostic biomarker and therapeutic target, demonstrating how traditional experimental validation coupled with computational prediction enhances translational potential. The multi-scale approach spanning bulk transcriptomics, AI-driven biomarker selection, single-cell characterization, and functional validation represents an effective paradigm for developing clinically relevant cancer biomarkers and therapeutic targets.

Pharmacological disruption of this N-terminal interaction by streptonigrin, in combination with standard chemotherapy, extended overall survival in a xenograft model of ovarian cancer. This study identified TGase 2 as a pivotal regulator of EMT-driven metastasis and drug resistance.

The results demonstrated that GBM-derived EVs significantly contribute to astrocyte phenotypic alterations associated with invasion and metastasis. These findings highlight the importance of EV-mediated intercellular communication in GBM progression and suggest further in vivo studies to elucidate their role in central nervous system invasion.

Notably, we identified a protein interaction between TGM2 and HK1 that was significantly upregulated in the papillary thyroid carcinoma cell line TPC-1. ProteoAutoNet provides an improved framework for investigating protein-protein interactions and uncovering interactions.

This patent describes novel substituted aryl sulfonamides and sulfuric diamides as potent transglutaminase 2 (TG2) inhibitors. It provides details on the novel substituted aryl sulfonamide and sulfuric diamide compounds, pharmaceutical formulations, and the use of such compounds in the treatment of TG2-related diseases, such as fibrosis, neurodegenerative diseases, autoimmune diseases, and cancers.