RAP1A (RAP1A, Member Of RAS Oncogene Family)

Antitumor efficacy in vivo was also observed with CML-07-119 in a mouse xenograft model engrafted with AML NOMO-1 cells, equivalent to the drug cytarabine...These structures revealed that the inhibitor occupies a previously proposed product inhibitory channel of the enzyme, and modulates previously unknown conformational states of GGPPS quaternary structure. This work validates GGPPS inhibition as potential novel mechanism for the treatment of AML.

Given the lack of targeted therapies for basal-subtype LUSC, RAPGEF3 emerges as a novel and promising therapeutic target. These findings not only contribute to understanding the molecular mechanisms of basal-subtype LUSC but also suggest that RAPGEF3-targeted therapies may be applicable to other cancers with similar oncogenic signaling pathways.

By combining microarray analysis, machine learning, and molecular docking, we identified five key target genes associated with DOX-induced cardiotoxicity. Functional analysis further suggested the involvement of the Rap1 signaling pathway and immune system regulation in DOX-induced cardiotoxicity. These findings offer insights into the molecular mechanisms underlying DOX-induced cardiotoxicity and have implications for the development of protective strategies and therapeutic interventions.

Together, these findings redefine the roles of Rap1A and Rap1B in endothelial biology and highlight their relevance in diseases such as tumor angiogenesis, atherosclerosis, and inflammatory lung injury. We discuss the therapeutic implications of targeting Rap1 isoforms in vascular pathologies and cancer, emphasizing the need for isoform-specific strategies that preserve endothelial homeostasis.

Functionally, CATED enhances cisplatin resistance by promoting cell proliferation and inhibiting apoptosis in vitro and in vivo...This study newly identifies a sEV-transmitted lncRNA CATED in driving HGSOC platinum-resistance and elucidates the mechanism it regulates the interacting protein through SUMOylation. These findings also provide a novel strategy for improving chemotherapy in HGSOC by targeting CATED.

Collectively, the mechanism underlying the synergistic action of IFN-γ and TNF-α is still lacking. Future work is needed to explore the crosstalk pathways of IFN-γ and TNF-α involved in the regulation of endothelial barrier function such as modulation of extracellular matrix (ECM) structure, involvement of tyrosine kinases and roles of small GTPases.

These findings confirm the effect of these variants on increasing the binding affinity of RAF1 to RAP1P. These mutations can therefore be targeted for cancer therapy to modulate the activity of the MAPK/ERK signaling pathway.

The TNM stage, microvascular invasion, Milan criteria, treatment and recipient KRAS rs712 genotype were independent factors for the RFS of LT patients. Recipient KRAS rs712 polymorphism is associated with HCC recurrence after liver transplantation and plays as a promising bio-predictor of overall survival rate of HCC risks after hepatic transplantation.

The Lucena 1 cell line, derived from the human chronic myeloid leukemia cell line K562 under selective pressure of vincristine supplementation, exhibits multidrug resistance (MDR)...This study offers new insights into the MDR phenotype and its multifactorial consequences in cellular pathways. Thus, unraveling the mechanisms of MDR holds promise for innovating cancer models and antitumor targeted strategies, since inhibiting the P-glycoprotein (P-gp)/ABCB1 protein is not always an effective approach given the associated treatment toxicity.

In conclusion, VASP emerges as a promising diagnostic and prognostic marker for OSCC within HNSCC, emphasizing the importance of exploring its regulatory mechanisms and therapeutic applications. The revealed pathways present avenues for targeted treatment in OSCC. Despite limitations, this study provides valuable insights with potential implications for improving patient outcomes.

Finally, we confirmed that the effects of cholesterol on melanoma resistance require its metabolite 27HC through CYP27A1 catalysis, and that 27HC further upregulates Rap1A/Rap1B expression and increases AKT phosphorylation. Thus, our results suggest that targeting 27HC may be a useful strategy to overcome treatment resistance in metastatic melanoma.

Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.