PSMD14 (Proteasome 26S Subunit, Non-ATPase 14)

Both genetic knockdown and pharmacological inhibition of PSMD14 recapitulate EB's effects, confirming its essential role in leukemia cell survival and proliferation. Collectively, these findings uncover a previously unrecognized PSMD14-AKT1/CDK4 regulatory axis in leukemia and position EB as a promising chemical probe and lead compound for the development of targeted covalent inhibitors against oncogenic DUBs.

PSMD14-IMPDH2 axis serves as a crucial hub integrating post-translational modifications and metabolic homeostasis in GBM. Targeting PSMD14 enhances therapeutic sensitivity, presenting a promising strategy to overcome TMZ resistance and improve GBM treatment efficacy.

Notably, combining circUBR5-targeting antisense oligonucleotides with cisplatin synergistically inhibited tumor growth and reversed chemoresistance in vivo. Thus, circUBR5 promotes GSRCC progression through dual pathways coordinating estrogen signaling and cholesterol metabolism, and its exosomal dissemination facilitates chemoresistance induction within the tumor microenvironment, highlighting its potential as a prognostic biomarker and therapeutic target.

The PSMD14 inhibitor Capzimin exhibited potent anti-tumor effects in vitro and in vivo, and combination therapy with the TGF-β inhibitor galunisertib demonstrated enhanced efficacy...Consequently, the PSMD14-HMMR axis emerges as a promising therapeutic target. Inhibition of PSMD14 exhibited significant anti-tumor efficacy, underscoring its potential for clinical translation in LUAD treatment.

Notably, high-throughput screening of FDA-approved drugs reveals that Daclatasvir (DCV) exhibits high binding affinity for PSMD14 protein, disrupts the PSMD14-PFKFB2 interaction, reduces PFKFB2 activity and tumor burden. Collectively, our findings are the first to elucidate a positive feedback loop existing between PSMD14 and glycolysis in GAC progression, suggesting that PSMD14 blockade may represent a potential therapeutic approach for GAC.

This study reveals a previously unrecognized role of PSMD14-derived lactate in mediating histone lactylation-coupled lipid deposition and tumor progression. Therapeutic co-targeting of PSMD14 and glycolytic lactylation significantly suppresses tumor growth in patient-derived xenograft models, suggesting a promising combinatorial strategy for pancreatic cancer treatment.

PTC 209 utilizes the high affinity of modified hyaluronic acid nanoparticles for colorectal cancer to reverse CSC stemness in colorectal cancer...These strategies emphasize specificity, nanodelivery, and combination therapies to reduce toxicity and resistance, highlighting precision oncology potential. Clinical validation remains critical for translation.

This study establishes PTM networks as central regulators of CRC progression and immune resistance. The PTM-AS framework enables precision subtyping, while GALNT6 emerges as a novel therapeutic target for overcoming immunotherapy resistance.

In vivo validation confirmed that PSMD14 knockdown suppressed tumor growth via SP1-GYS1 axis disruption. This work establishes MRPM as a robust predictive tool and elucidates the PSMD14-SP1-GYS1 regulatory network as a potential therapeutic target in melanoma metabolism.

The rapid degradation of the cancer driver PPM1D is achieved through direct recognition by the proteasome, and proteasome inhibitors may reduce therapeutic efficacy due to the accumulation of PPM1D. PPM1D may serve as a suitable model substrate for elucidating the mechanism of ubiquitin-independent proteasomal degradation and represents a potential novel therapeutic target for cancer treatment based on proteasome inhibition.

Higher serum HSPA9 was linked to shorter overall survival rate and independently predicted poor prognosis. Our study demonstrated that elevated serum HSPA9 protein serves as a potential biomarker for bortezomib resistance and poor prognosis in MM patients.

Furthermore, PSMD14 also activated the PI3K/AKT/mTOR pathway and enhanced cellular sensitivity to Cisplatin. Collectively, our findings demonstrate that PSMD14 promotes breast cancer progression through dual mechanisms: deubiquitination of FOXM1 and activation of the PI3K/AKT/mTOR pathway. Thus, PSMD14 represents a potential therapeutic target for breast cancer intervention.