TGM2 (Transglutaminase 2)

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.

Finally, investigations into the neuro-immune axis highlight the dual roles of adaptive immunity in Alzheimer's disease and evaluate novel pharmacological modulators targeting the kynurenine-aryl hydrocarbon receptor (AhR) axis. Collectively, this Special Issue delivers groundbreaking insights and innovative strategies aimed at restoring biological homeostasis and overcoming intractable diseases.

As a result, TG2 plays a role in developing drug resistance, acting as a primitive systemic defense mechanism linked with survival signals. I suggest that blocking TG2 binding, combined with inhibiting autophagy or alternative signaling pathways, is essential for effectively overcoming drug resistance, since it is rooted in TG2's primordial role.

Meningioma brain invasion is defined by molecular remodeling of tumor cells and functional interactions within the tumor microenvironment.

Lastly, TGM2 and P2RX7 form a positive feedback regulatory loop, jointly regulating Glu metabolism and mitophagy, thereby promoting drug resistance in Gem-R PDAC cells. These data suggest that the TGM2-P2RX7 loop promotes Gem-R in PDAC by improving Glu metabolism and mitophagy, highlighting its potential as a crucial therapeutic target for PDAC.

Clinical data reveal GBM patients with an SDC1 valine 225 or aspartate 228 mutation display lower response to radiotherapy. In this study, we disclose the critical role of NK cells in tumor radiotherapy through secreting GZMB and impeding autophagosome maturation, as well as propose a potential strategy combining radiotherapy and NK-based immunotherapy against radioresistant GBM.Abbreviations: DEGs: differentially expressed genes; GBM: glioblastoma; GZMB: granzyme B; IL: interleukin; IR: ionizing radiation; IRS: immunoreactive score; LAMP: lysosomal associated membrane protein; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; mSDC1: mutant SDC1; NK: natural killer; PRF1: perforin 1; SDC1: syndecan 1; SNAP29: synaptosome associated protein 29; SQSTM1: sequestosome 1; STX17: syntaxin 17; TGM2: transglutaminase 2; TME: tumor microenvironment; TGD: tumor growth delay; VAMP8: vesicle associated membrane protein 8; WT: wild type.