MAGEE1 (MAGE family member E1)

These dual roles are mediated by extracellular acidification, HCAR1, and lactylation. Given that duality, we suggest that redirecting lactate flux presents considerable potential as a therapeutic approach for the prevention and management of OA.

This study introduces a novel artificial intelligence-based framework for HCAR1-targeted drug discovery and highlights potential lead compounds for further development.

These findings expand our understanding of HCAR1 signalling and introduce new molecular tools for probing its physiological and pathological roles. The characterized ligands may support future therapeutic strategies targeting HCAR1 in metabolic disorders while informing approaches to mitigate potential oncogenic effects.

The ability of nuclear GPR81 to directly regulate gene expression, combined with extracellular matrix -mediated mechanical signaling, creates a potentially robust system for the coordinated adaptation and survival of cancer cells. Understanding these interactions could lead to the discovery of new therapeutic targets and improved treatment strategies for cancer.

Therefore, this review summarizes recent advances in the structural features, subcellular localization, biological functions, and molecular mechanisms of hCaf1 isoenzymes, with a focus on their roles in tumor progression. This work aims to facilitate a comprehensive understanding of hCaf1 family deadenylases.

HCAR1 mediates lactate-driven ferroptosis resistance in GC through the AMPK-SCD1 signaling pathway. Targeting the HCAR1-lactate axis may offer a promising strategy for overcoming metabolic adaptation and improving GC treatment outcomes.

Moreover, the combination of Endothall and Cisplatin is high synergistic in treating OS. In conclusion, the study elucidates the pro-oncogenic role of lactate-activated HCAR1 in OS.

In a CT26 liver metastasis model, PFSUV-IMQ combined with Oxaliplatin reduced tumor size, increased CD8+ T cell infiltration, and enhanced tumor apoptosis. RNA-seq shows enrichment of innate immune activation genes after a single dose. These findings suggest that targeted IMQ delivery activates the tumor immune microenvironment, leading to reduced tumor burden in liver cancer and metastasis models.

It exerted its effects by regulating the GPX4/SLC7A11 axis to inhibit lipid peroxidation and malondialdehyde accumulation, thereby obstructing ferroptosis. Experimental validation demonstrated that the downregulation of HCAR1 promoted ferroptosis and suppressed malignant tumor phenotypes, suggesting that both the gene and its associated risk model hold significant clinical value as potential therapeutic targets and prognostic biomarkers.

Established tumors were treated with a STING agonist (BMS-986301) or anti-PD1 ICB, and mice were followed to evaluate safety and efficacy, as well as the mechanisms of treatment resistance by RNA sequencing, flow cytometry, and immunofluorescence, B-cell depletion and T-cell immunoglobulin and mucin domain 1 (TIM-1) ICB...This approach decreased the number of TIM-1+ B cells in the tumor and shifted B cells to higher expression of CD86 and MHC class II, enhancing the antigen presentation capability and further boosting the antitumor efficacy of CD8+ cytotoxic T cells. Conclusion : Our findings demonstrate that B cells are associated with ICB- and STING-mediated therapy resistance, and that depleting B-cells or targeting TIM-1 enhances both innate and acquired therapeutic efficacy in HCC.

Here, we report four cryo-EM structures of human HCAR1 and HCAR2 in complex with the Gi1 protein, in which HCAR1 binds to the subtype-specific agonist CHBA (3.16 Å) and apo form (3.36 Å), and HCAR2 binds to the subtype-specific agonists MK-1903 (2.68 Å) and SCH900271 (3.06 Å)...On this basis, we further summarize the structural features of agonists that match the orthosteric pockets of HCAR1 and HCAR2. These structural insights are anticipated to greatly accelerate the development of novel HCAR1-targeted drugs, offering a promising avenue for the treatment of various diseases.

Our findings demonstrate that B cells are associated with ICB- and STING-mediated therapy resistance, and that depleting B-cells or targeting TIM-1 enhances both innate and acquired therapeutic efficacy in HCC.