USP47 (Ubiquitin Specific Peptidase 47)

Limiting PA intake or targeting the ACSL5/COX2/EP4 axis enhanced paclitaxel efficacy in a breast cancer mouse model. Collectively, these findings highlight the critical role of PA and ACSL5/COX2/EP4 signaling in lung metastasis, which can act as promising targets for enhancing the efficacy of chemotherapy in BC patients with lung metastasis.

Bioinformatics analysis demonstrates that these DUBs except USP47 are upregulated and overall survival analysis indicates that lower expression of these DUBs, except USP37 and USP49, is correlated with improved overall survival in lung cancer patients. These findings strongly suggest that DUBs may play a crucial role in overcoming cisplatin resistance and improving the treatment efficacy for lung cancer.

Remarkably, N1 inhibits HH-MB growth in vitro and in vivo, crosses the blood-brain barrier, and improves survival in a HH-MB mouse model. These findings highlight N1 as a breakthrough ERAP1 inhibitor and provide a promising therapeutic option for the treatment of HH-dependent cancers.

Furthermore, we summarize recent advances in the development of USP47 inhibitors and propose promising directions for future therapeutic targeting. Overall, this review highlights the important yet still underexplored roles of USP47 in multiple disease pathways.

Additionally, USP47 enhances angiogenesis by stabilizing NRP1, preventing its ubiquitination and degradation, and activating the PI3K/Akt signaling pathway. These results suggest that USP47 contributes to GC progression through the regulation of NRP1-mediated angiogenesis, highlighting its potential as a therapeutic target for GC treatment.

USP47 is essential for modulating proliferation, migration, invasion, and immune evasion of HCC cells. Inhibiting USP47 in combination with PD-1 blockade can enhance the suppression of HCC growth, potentially holding clinical importance. This investigation elucidates the role of USP47 in PD-L1 stability via deubiquitination, offering a new prognostic indicator and potential target for treating HCC.

Furthermore, USP47 inhibition-either by siRNA knockdown or K-552 treatment-enhances the efficacy of Sotorasib in vitro and in vivo. Together, our findings establish USP47 as a promising therapeutic target in KRASG12C-mutated NSCLC and introduce K-552 as a USP47 inhibitor with potential for combination therapy with KRASG12C inhibitors.

Furthermore, we identify Snai1 as a deubiquitination target of USP47, explaining USP47-dependent activation of epithelial-mesenchymal transition pathway and tumor progression. Our findings identify an important genetic predisposition that implicates the perturbation of transcription and proteostasis programs in GC, offering insights into prevention and therapeutic strategies for genetically stratified patients.

Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

JOSD2 plays a crucial role in enhancing the proliferation, migration, and drug resistance of ESCC, suggesting that JOSD2 is a potential therapeutic target in ESCC.

This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells.