CTSG (Cathepsin G)

Targeting SERPINA3 with antisense oligonucleotides successfully sensitized liver cancer cells to irinotecan therapy. These findings elucidate a critical mechanism of chemoresistance in liver cancer and propose targeting SERPINA3 as a promising therapeutic strategy to enhance chemotherapy efficacy.

These protease-mediated mechanisms represent the earliest interventional window in metastatic progression, offering therapeutic potential to prevent niche formation rather than treat established metastases. However, significant methodological challenges remain, including the need for organ-specific biomarkers, improved in vivo methods for measuring protease activity, and a better understanding of temporal PMN dynamics across different target organs.

This study demonstrated a causal effect of CTSS on DLBCL based on the MR algorithm. Follow-up studies are needed to elucidate the underlying mechanisms between them and explore promising new therapeutic options for DLBCL patients.

These enzymes also influence NET formation, linking classical lysosomal proteolysis to specialized immune responses. This review synthesizes current evidence on cathepsin-mediated regulation of neutrophil effector functions, highlighting their dual role in host defense and disease pathology, and discusses their potential as therapeutic targets for mitigating NET-driven inflammation in conditions such as autoimmune diseases, cancer metastasis, and ischemia-reperfusion injury.

In neutrophils, Click-CLOZ bound proteins included MPO, S100, and DEFA1B, which are also associated with neutrophil-mediated oxidative stress and immune responses. In conclusion, the application of click chemistry proteomics has facilitated a novel approach to identify multiple clozapine-bound protein targets that will be used to advance our understanding of the toxicity of clozapine.

Our previous study revealed that CB-839 and 5-FU-treated colorectal cancer (CRC) tumors recruited neutrophils and induced neutrophil extracellular traps (NETs)...Inhibiting CDK1 protected CRC cells from killing by CTSG. Our study reveals novel mechanisms by which CTSG enters and kills CRC cells.

109 neutrophil mRNA transcripts and 20 neutrophil granule proteins were upregulated in platelets of MPN patients compared to controls, including cathepsin-G (CTSG) and LTF, with 5.1- and 4.6-fold increase in mRNA and 1.8- and 1.4-fold protein increases respectively. This suggests the transfer of neutrophil material occurs during emperipolesis in disease state, which could be a consequence of neutrophil degranulation or apoptosis.

These results suggest that quercetin and trigonelline are partly responsible for the inhibitory effect of fenugreek on cathepsin G-induced malignant progression of human breast cancer cells. Our findings provide a new breast cancer treatment strategy targeting cathepsin G, and fenugreek may have synergistic effects when combined with therapeutic drugs.

Importantly, we found that CG1/A2-CAR T cells did not affect normal bone marrow hematopoiesis. These results validate signal peptides as immunotherapeutic targets and provide a foundation for the continued clinical development of CG1/A2-CAR T cells in AML and CML.

Lastly, CG1/A2xCD3 had no activity against normal bone marrow. Together, these results support the targeting of LS-derived peptides and the continued clinical development of CG1/A2xCD3 in the setting of AML.

This study confirmed a direct link between cathepsins and the risk of renal cancer. Specifically, cathepsin S has a significant positive correlation with the risk of pRCC. The findings of our research could provide significant contributions to both fundamental and clinical investigations pertaining to renal cancer. Key message What is already known on this topic? - Previous studies have suggested the role of some cathepsins in renal cancer occurrence and progression. However, the causal link between different cathepsins and renal cancer is unknown. What this study adds? - Our Mendelian randomization (MR) study revealed that the effects of different cathepsins on the risk of renal cancer. Remarkably, both univariable MR and multivariable MR demonstrated that the levels of cathepsin S increases the risk of papillary renal cell carcinoma. How this study might affect research, practice or policy? - The findings offer novel insights into the relationship between cathepsins and renal cancer, which may have implications for the prevention and management of renal cancer.

In conclusion, our study reveals that GPRC5A plays an unexpected role in regulating keratinocyte behavior, with implications for its C-terminal region translocation into the nucleus. These results offer promising avenues for future research in the field of wound healing.