SLIT2 (Slit Guidance Ligand 2)

Enhanced antigen presentation and epithelial proliferation likely facilitate tumor-immune interactions, contributing to better clinical outcomes. This study advances the understanding of TME dynamics in OPSCC and may inform future therapeutic strategies.

revealed that tumors hijack an interorgan nociceptor-slit guidance ligand 2-calcitonin gene-related peptide circuit to escape immune surveillance. Disrupting this neural loop restores T-cell function and enhances immunotherapy efficacy.

• Reproducible analysis: standardized thresholds for TRIC hits and relative IC50 reporting for partial inhibitors. • Generalizable to other extracellular glycoproteins and ligandable protein-protein interactions (PPIs).

Molecular docking with validated hits revealed a shared ROBO2 binding pocket defined by conserved anchor residues (ASN354, SER366, ASP385) and accommodation of distinct ligand conformations within the ROBO2 binding pocket. This work establishes a screening pipeline for identifying ROBO2-targeted small molecules and lays the foundation for developing therapeutics aimed at disrupting Slit-ROBO2 signaling in GBM.

The MBRG-based model effectively predicts BLCA prognosis, integrates mechanisms of basement membrane remodeling, EMT, and immune suppression, and identifies DDR2 and SERPINF1 in CAFs as potential targets for personalized therapy.

Notably, both recombinant SLIT2 and SP5 confer hepatoprotection even when administered 24 hours after APAP challenge. These findings suggest that SLIT2/ROBO4-targeted therapies may offer a promising approach for preventing fulminant hepatitis in the context of toxic liver injury.

This study highlights the potential of FZD1 as a biomarker for predicting fibrotic status in patients with GC and the SLIT2‒ROBO1 axis as a therapeutic target to reverse a fibrotic and immunosuppressive TME.

Our study identifies a novel DAP12-dependent mechanistic link between upregulated Slit2 expression in excitatory neurons and oligodendrocyte-dependent myelination loss in tauopathy. Despite elevating tau load, the absence of microglial Dap12 ameliorates neuroinflammation and improves brain functions in tauopathy mice. Our study suggests that selectively targeting the toxic aspects of DAP12 signaling while preserving its beneficial functions may be a promising strategy to enhance brain resilience in AD.

These results suggested that targeting SLIT2 pathways could represent a novel therapeutic strategy for LUAD and further research is needed to explore the specific mechanisms through which SLIT2 exerts its tumor-suppressive effects and modulates immune responses. The current study enhances the understanding of LUAD biology and underscores the potential of SLIT2 as a biomarker and therapeutic target in LUAD.

The lead peptide SP4 also demonstrated favorable in vitro pharmacokinetic properties, including strong stability in simulated intestinal fluid, high plasma integrity, and moderate metabolic stability in rat liver microsomes. Collectively, this work establishes a computational-to-experimental pipeline for discovering macrocyclic peptides that disrupt challenging protein-protein interactions and provides a foundation for developing next-generation SLIT2/ROBO1 modulators for cancer and neuroimmune disorders.

The p53 reactivator APR-246 restores sensitivity of p53R273H-expressing cells to LT1-3. Therefore, LT1-3 possesses multifunctional antitumor properties, directly inhibiting tumor cells and enhancing the efficacy of cisplatin, without causing toxicity to normal cells. Combining LT1-3 with cisplatin holds promise as a first-line therapy for lung cancer, while LT1-3 alone may be suitable for maintenance therapy.

This study elucidates the synergistic regulatory mechanisms between fibroblasts and keratinocytes within the tumor microenvironment of ESCC. These findings offer a novel theoretical foundation for molecular classification, prognosis prediction, and precision treatment of ESCC.