Disease relevance of SLIT1

• To our knowledge, this is the first report to analyze in detail the effect of Slit on breast cancer cell motility as well as its effect on the critical components of the cancer cell chemotactic machinery [1].
• Studies of the Slit-Robo complex may foster new anti-chemotactic approaches to block cancer cell metastasis [1].
• In contrast, the expression of slit2 mRNA increased in most of the malignant mammary tumors, and an increase in slit3 mRNA expression was observed in 2 of the malignant mixed tumors [2].
• Inhibition of medulloblastoma cell invasion by Slit [3].
• Dynamic changes in Robo2 and Slit1 expression in adult rat dorsal root ganglion and sciatic nerve after peripheral and central axonal injury [4].

Psychiatry related information on SLIT1

• A recent report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette Syndrome (TS) [5].

High impact information on SLIT1

• They also support a common guidance mechanism for axon projection and neuronal migration and suggest that Slit may provide a molecular tool with potential therapeutic applications in controlling and directing cell migration [6].
• Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand [7].
• Here, the guidance ligand Slit and its receptor Robo control not whether axons cross (as in other midline decisions), but where the chiasm forms [8].
• Interestingly, Slit also appears to use Roundabout to control leukocyte chemotaxis, which occurs in contexts different from neuronal migration, suggesting a fundamental conservation of mechanisms guiding the migration of distinct types of somatic cells [9].
• Mutation of conserved basic residues in the C-terminal cap region of Slit D2 reduces heparin binding and abolishes biological activity [10].

Biological context of SLIT1

• We also show that Slit treatment inhibits CXCL12/CXCR4-induced breast cancer cell chemotaxis, chemoinvasion, and adhesion, the fundamental components that promote metastasis [1].
• We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs) in CC cell lines failed to effectively reactivate the down-regulated expression [11].
• Here we show that the second leucine-rich repeat domain (D2) of Slit, which mediates binding to Robo receptors, also contains a functionally important binding site for heparin, a highly sulfated variant of HS [10].
• Potential role of the Slit/Robo signal pathway in angiogenesis [12].
• Sciatic transection resulted in a significant up-regulation of both Robo2 and Slit1 mRNA and protein (p<0.05 versus control) [4].

Anatomical context of SLIT1

• Our results therefore indicate that Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis [13].
• In the present study, we observe that both Slit1 and Slit3 repel and inhibit neurite growth of fetal DA neurons [14].
• Retinal growth cone collapse triggered by Slit D2 requires cell surface HS or exogenously added heparin [10].
• Here, we show that slit1 and slit2, known chemorepellents for RGC axons expressed in specific regions of the diencephalon and telencephalon, help regulate optic tract development [15].
• Sciatic nerve transection also led to an accumulation of Slit1 protein in peripheral region of the traumatic neuroma [4].

Associations of SLIT1 with chemical compounds

• Structural determinants of heparan sulfate interactions with Slit proteins [16].
• At this time interval an effect on methacholine challenge was also seen in SLIT 3 [17].
• EXPERIMENTAL PROCEDURES: Slit-lamp biomicroscopy and fluorescein angiography; confirmation of vitreomacular relationship with B-scan ultrasonography, optical coherence tomography (OCT), or both [18].

Physical interactions of SLIT1

• We demonstrate that the mouse SLIT1 protein can bind ROBO1, a transmembrane receptor implicated in axon guidance [19].

Analytical, diagnostic and therapeutic context of SLIT1

• However, unlike fetal DA neurites, no directed neurite outgrowth was observed in the cocultures of ES-derived DA neurons with Netrin-1-, Slit1-, and Slit3-producing cells [14].
• Analytical gel filtration chromatography demonstrates that Slit D2 associates with a soluble Robo fragment and a heparin-derived oligosaccharide to form a ternary complex [10].
• These competition studies demonstrate that the smallest heparin oligosaccharide competing with heparin binding to Slit was a tetrasaccharide, and that in the ELISA maximum inhibition (approximately 60% at 2 microM concentration) was attained with a dodecasaccharide [16].
• In conclusion, we report an altered expression and redistribution of Robo2 and Slit1 in the DRG and sciatic nerve trunk after peripheral axotomy [4].
• By contrast, injury to the central axons of the DRG by dorsal rhizotomy did not up-regulate Slit1 and Robo2 expression [4].

References