ROBO2 (Roundabout Guidance Receptor 2)

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.

ROBO2 and GPR180/CG9304 were down and upregulated, respectively, in flies and patients with RAF fusions. Our study provides mechanistic insights into pLGG tumorigenesis and suggests targeting repulsive guidance signaling and GPR180/CG9304 as potential therapeutics for pLGG subtypes.

This study investigated three CDKis (abemaciclib, fadraciclib, and dinaciclib) alone or combined with retinoic acid (RA) to assess the effects on morphology, growth, gene expression, and the induction of immunogenic cell death in NB cell lines with (LAN-1 and CHLA-90) and without (CHLA-172) MYCN amplification. CDKi treatments promote NB differentiation via ER stress, with cytotoxicity enhanced by RA co-treatment. This may increase NB immunogenicity and support immunotherapy eligibility.

Molecular dynamics simulations suggested potential direct interactions between PDGFB and osimertinib, providing additional insights into the resistance mechanism. Our study identifies a novel circROBO2/miR-625-5p/PDGFB regulatory axis in osimertinib resistance and positions circROBO2 as a potential therapeutic target and biomarker for NSCLC treatment.

To understand the development of adult glioma, we demonstrate that D2HGDH and PHLDB1 should be prioritized for functional studies in IDHmut tumors. The ROBO1 region warrants further investigation in IDHwt tumors.

Genomic complexity was significantly higher in EMD samples compared to BMA, as evidenced by increased tumor mutational burden and the enrichment of 1q gain/amplifications. These findings highlight the distinct molecular profile of EMD compared to BMA and highlighted the genomically complex and heterogeneous nature of extramedullary tumors.

Notably, natural selection analysis and functional validation indicate an adaptive variant with higher Slit1 gene expression in the Tibetan population, which has low oxygen availability. Collectively, these findings show a neuronal Slit1-dependent program of OL differentiation and suggest that targeting the Slit1-Robo2 signaling axis may have therapeutic potential for treatment of preterm infants with hypoxic WMI.

Heterogeneity in the hormone receptor and HER2 status of SBBC poses unique therapeutic challenges. Future studies should aim to identify the optimal management strategy for this disease.

Metabolic pathway analysis revealed glutathione metabolism and glutamate metabolism are the pathways most enriched with significant metabolites related to LC. These findings underscore the importance of GM in the development of LC, with metabolites partly mediating this effect, and provide dietary and lifestyle recommendations for high-risk lung cancer populations.

The expression of Robo2 and other cell surface molecules, such as Teneurins or the Ephrin receptor is regulated by fate-patterning pathways intrinsic and extrinsic to the wing disc, as well as by expression of oncogenic RasV12. Combined, we demonstrate that neighboring cells respond to a mismatch in surface code patterns mediated by specific transmembrane proteins and reveal a novel function for these cell surface proteins in cell fate recognition and removal of aberrant cells during development and homeostasis of epithelial tissues.

High-throughput sequencing and validation experiments verified that YB-1 was the downstream target gene of Robo2, and over-expression of YB-1 could reverse the apoptosis induced by Robo2 down-regulation and its inhibitory effect on EMT and proliferation. Robo2 deficiency inhibits EMT and proliferation of hepatoma cells and augments the cell apoptosis by regulating YB-1, thus inhibits the occurrence of HCC and provides a new strategy for the treatment of HCC.

These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.