Notably, pharmacological inhibition of Rac1 activation with NSC23766 abolished OTUB2-mediated hypertrophic responses in PE-treated cardiomyocytes. Our findings establish the OTUB2/Rac1 axis as a novel regulator of pathological cardiac hypertrophy and a potential therapeutic target for cardiac remodeling.

This study identifies the Rac1-USP11 reciprocal feedback loop as a novel, self-reinforcing mechanism driving radioresistance in HCC. Targeting this loop via combined Rac1-GTP/USP11 inhibition represents a promising therapeutic strategy for radiosensitizing HCC.

Expression of myogenesis and inflammation markers, GLUT4 translocation, [3H]2-deoxyglucose uptake, and intramyocellular insulin signalling were determined...Moreover, breast cancer CM inhibits basal and insulin-mediated GLUT4 translocation and glucose uptake, likely by blocking insulin-stimulated Rac1, but not Akt-TBC1D4 activation. These results underscore a potential mechanistic link between breast cancer and metabolic disorders and suggest that skeletal muscle rewiring may play a role.

NSC23766, a RAC1 GTP inhibitor, was employed to identify the pathway-specific effects...RAC1 overexpression portends poor HCC prognosis and mediates radioresistance through GTP-dependent activation of antiapoptotic pathways and cell cycle modulation. Targeting RAC1 GTP activity may enhance the radiosensitivity of HCC.

RAC1 genetic or GYS32661 mediated inhibition leads to RAC1 dissociation from the GLI1 promoter and transcriptional repression of Shh-MB biomarkers GLI2, DNMT1 and UHRF1. This eventually causes inhibition of Shh-MB tumor cell proliferation and migration, which leads to a decrease in Shh-MB development.

The translational relevance of these findings is underscored by the growth inhibition observed in patient-derived BPH organoids treated with NSC23766. In conclusion, our findings identify TIAM1 as a key driver of prostatic branching and growth, and suggest that targeting TIAM1-RAC1 signaling could be a promising therapeutic strategy for BPH.

P1, N=48, Recruiting, MBQ Pharma | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

Importantly, inhibition of Rac1 GTPase activity with NSC23766 significantly reduced DHA-mediated haemolysis, as did co-administration of either sucrose or polyethylene glycol 8,000. Conversely, the presence of 125 mM KCl and urea without extracellular Ca2+ significantly exacerbated DHA toxicity. In conclusion, this is the first report that identifies key biochemical mechanisms underlying the cytotoxic effects of DHA in RBCs, promoting further development and validation of DHA in anticancer therapy.

Notably, co-treatment of cells with GAL and staurosporin, D4476, or acetylsalicylic acid prevented PS externalization whereas only the presence of SB203580 and NSC23766 rescued the cells from GAL-induced hemolysis. Ca2+ nucleation and metabolic collapse mediated by PKC/CK1α/COX/p38/Rac1 drive GAL-induced eryptosis and hemolysis. These novel findings carry ramifications for the clinical prospects of GAL in anticancer therapy.

Mechanistically, RACK1 increased the expression of FUT8 by inhibiting miR-1275, which in turn promoted the FUT8-catalyzed core-fucosylation of cystine/glutamate antiporter SLC7A11, thereby inhibiting SLC7A11 degradation and cell ferroptosis. Our data highlight the role of RACK1 in cervical cancer progression and its suppression of ferroptosis via the RACK1/miR-1275/FUT8/SLC7A11 axis, suggesting that inhibiting this pathway may be a promising therapeutic approach for patients with cervical cancer.

Moreover, inhibition of Rac1 by EHT-1864 or azathioprine in mice models can remarkably alleviate IBSP-induced BM of lung cancer. Overall, our study suggests that tumor-secreted IBSP promotes BM by inducing macrophage-to-osteoclast differentiation, with potential as an early diagnostic maker for BM, and Rac1 can be the therapeutic target for IBSP-promoted BM in lung cancer.

Mechanically, the TIAM1-RAC1(T lymphoma invasion and metastasis-inducing protein 1-Ras-related C3 botulinum toxin substrate 1) axis participates in the progression of AAD induced with S-nitrosylated septin2. More importantly, developing R-ketorolac and NSC23766 compounds that specifically target the TIAM1-RAC1 pathway may be new a potential strategy for alleviating AAD.