PAK2 (P21 (RAC1) Activated Kinase 2)

Future research should focus on elucidating the spatiotemporal dynamics of these mechanisms and integrating immunotherapy with molecular targeting to improve outcomes for PC patients with hepatic metastasis. This review aims to provide a reference for the mechanism research and therapeutic intervention of hepatic metastasis of pancreatic cancer (HMPC).

The kinases PAK1 and PAK2 shield RAS from LZTR1-dependent degradation by phosphorylating T148, and targeting PAK1/2 activity improves RAS-directed therapy. Collectively, our findings reveal a novel regulatory circuit governing RAS stability that is preferentially active in blood cancers and potentially druggable.

Furthermore, PP1 and PP2A activation is needed for Na+, K+-ATPase activation, which mediates pancreatic acinar fluid and electrolyte secretion. These results support the conclusion that PP1and PP2A play an important role in pancreatic acinar fluid and electrolyte secretion, mediated by a PAK4-dependent mechanism, with when combined with their recent described roles in pancreatic enzyme secretion, pancreatitis and pancreatic acinar growth and cancer, demonstrate they play important roles in both physiological and pathological responses in the exocrine pancreas, similar to their previous established roles in the endocrine pancreas.

Moreover, CXCL10 neutralization in mice reverses the vascular and immune changes induced by endothelial PAK2 deletion. Together, these findings identify endothelial PAK2 as a potential target to limit tumor angiogenesis and reprogram ECs to promote immune infiltration through CXCL10 signaling.

These findings established that melatonin suppresses neuroblastoma growth by mitigating Pak2‑mediated ER stress to induce cytotoxic autophagy. The present study provided novel insights into melatonin as a promising therapeutic agent for neuroblastoma, warranting further exploration in preclinical models and clinical trials.

This study revealed that PAK2 promotes CTC cluster formation and breast cancer metastasis by enhancing E-cadherin-mediated cell-cell adhesion. These results provide novel insights into the molecular mechanisms underlying CTC cluster formation and highlight PAK2 as a potential therapeutic target and diagnostic marker for preventing breast cancer metastasis.

The signature integrates non-invasively detected sEV RNAs to complement LDCT, addressing its high false-positive rate, and offers prognostic insights for personalized treatment strategies. These findings highlight the clinical potential of sEV-derived long RNAs in early LUAD detection and precision oncology.

Butein exhibits stable binding to the PAK2 protein, suggesting its potential as a targeted therapeutic agent. In summary, through multi-omics integration analysis, this study first reveals that PAK2 plays a central role in the pathogenesis of HNSC by regulating PCD, tumor stem cell properties, and the immune microenvironment, and provides a candidate drug for its targeted therapy.

Furthermore, we retrieved single-cell sequencing datasets for tumors from cancer patients and found that unbiased signatures identified here through proteomic analysis were able to separate proinflammatory macrophage populations in a clinical setting and could thus be used to expand state-specific markers. This study contributes to in-depth multi-omics characterizations of macrophage phenotypic landscapes, which could be valuable for assisting future interventions that therapeutically alter immune cell compartments.

In vivo PAK1 and PAK2 cooperate in restraining oxidative responses, and in maintaining cytokinetic fidelity and gut barrier integrity to safeguard from a macrophage-driven hematologic malignancy associated with low-grade inflammation. Targeted interference with PAK2 holds promise in immunotherapy by harnessing hyperphagia and SIRPA sequestration for accelerated cancer cell killing.

Notably, to our knowledge, this represents the first reported case of a benign poroma harboring a PAK3 rearrangement. These findings support a role for PAK gene fusions that may contribute to sebaceous differentiation in folliculosebaceous poroma and underscore the molecular heterogeneity of poromas.