RAC1 (Rac Family Small GTPase 1)

The oncogenic pattern of MUP showed a UV signature suggesting an origin in sun-exposed localisations. OS of MUP is comparable to melanoma of known cutaneous primary.

Endothelium-specific TBK1 knockdown or GSK8612 treatment inhibits EndMT and plaque formation. Safe TBK1 inhibitors could be developed into effective agents for the treatment of atherosclerotic vascular disease.

Thus, our data support a model in which cyclin D1/D2-CDK4 promotes phosphorylation of Smad3, leading to upregulation of integrin subunits, activation of FAK and Rac1, and consequent lamellipodia formation and cell migration. These findings provide direct evidence that CDK4 regulates actin cytoskeletal reorganization during cell migration and suggest that CDK4/6 inhibitors may dampen cytoskeleton-dependent tumor invasion, in addition to their antiproliferative effects.

Mechanistically, EHDPP binds to EGFR and inhibits its ubiquitination-mediated degradation, thereby stabilizing EGFR protein and partly activating the downstream PI3K-AKT signaling pathway, which ultimately promotes lung cancer cell proliferation and migration. This study is the first to elucidate the molecular mechanism underlying the pro-carcinogenic effects of EHDPP at the interaction level, providing potential molecular marker clues and mechanistic basis for EHDPP-related environmental risk assessment.

These findings expand the spectrum of DOCK2-related disease by showing that heterozygous pathogenic variants disrupting DOCK2-ELMO1 interactions impair protein stability and anti-viral immunity, revealing a previously unrecognized IEI affecting otherwise healthy individuals.

Entinostat, an inhibitor of class I HDAC, synergizes with cisplatin by preventing ARHGDIB delactylation. Collectively, our findings unveil a unique paradigm in which delactylation of tumor suppressors drives metastasis and chemoresistance. Targeting lactylation dynamics with HDAC inhibitors presents an avenue for intervention of bladder cancer.

Through comprehensive clinical cohorts and functional investigations, the present study identified TIPE2 as a clinically significant prognostic biomarker and revealed its potential role in regulating integrin-mediated oncogenic processes in cholangiocarcinoma. Therapeutic enhancement of TIPE2 expression emerges as a promising precision medicine strategy for cholangiocarcinoma management.

Critically, pharmacological inhibition abolished GGPPS-driven geranylgeranylation-dependent signaling: JSH-23 reversed both the proliferation mediated by RHOA and NF-κB p65 and the upregulation of IL1B potentiated by GGPS1 overexpression; and NSC23766 blocked the RAC1/STAT1-dependent IL1RAP activation amplified by GGPPS elevation, confirming that both axes are indispensable for GGPPS-dependent proliferation. Collectively, this GGPPS-mediated geranylgeranylation axis, converging on IL-1 pathway amplification, represents a central therapeutic vulnerability in LUSC, highlighting GGPPS as a promising macromolecular target for this recalcitrant malignancy.

Further treatment with CXCL5 ligand significantly induced neuritogenesis, while the neurite outgrowth was abrogated when cotreated with CXCR2 (receptor for CXCL5) inhibitor SCH527123...NR4A2 knockdown in UMSCC1 cells impaired tumor formation in vivo, and the xenograft tissues exhibited significant downregulation of CXCL5, providing direct in vivo evidence for the NR4A2-CXCL5 axis in tumor progression. NR4A2 is a key driver of CXCL5-mediated PNI and the NR4A2/CXCL5/CXCR2 signaling axis is a potential therapeutic target in HNSCC and PDAC.

Moreover, Rgnef-deficient mice were protected from bone loss caused by lipopolysaccharide-induced inflammation or ovariectomy. Thus, Rgnef is a crucial regulator of bone metabolism and could serve as a potential new target for treating bone diseases.

During epithelial chemotaxis, traction forces originate from internal cell-cell junctions, whereas in mesenchymal clusters, they remain peripheral. Our findings reveal that mesenchymal collective chemotaxis relies on supracellular force coordination, while epithelial chemotaxis depends on force generation by individual cells within the collective.

Collectively, these findings highlight persistent gaps, including limited integration with immuno-oncology and precision medicine frameworks and underexplored roles of non-canonical Rho GTPases. This bibliometric assessment provides a structured overview of three decades of research and identifies priorities to guide future investigations into Rho GTPase-driven cancer biology and therapy.