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Last update 23 Jan 2025

ROBO1

Last update 23 Jan 2025

Basic Info

Synonyms

Deleted in U twenty twenty, DUTT1, FLJ21882

+ [7]

Introduction

Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10102268, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). May be required for lung development (By similarity).

Drugs associated with ROBO1

Anti-ROBO1 CAR T cells(National Research Council Canada)

Target

ROBO1

Mechanism

ROBO1 inhibitors

Active Org.

McMaster University [+1]

Originator Org.

National Research Council of Canada [+1]

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Anti-ROBO antibody(Yale University School of Medicine)

Target

ROBO1 x ROBO2

Mechanism

ROBO1 inhibitors [+1]

Active Org.

Yale School of Medicine

Originator Org.

Yale School of Medicine

Active Indication

Neovascularization, Pathologic

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ROBO1 Specific BiCAR-NK/T cells(Asclepius)

Target

ROBO1

Mechanism

ROBO1 inhibitors

Active Org.-

Originator Org.

Asclepius Technology Company Group (Suzhou) Co., Ltd.

Active Indication-

Inactive Indication

Recurrent Carcinoma [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ROBO1

NCT03931720

/ Unknown statusPhase 1/2

Clinical Research of ROBO1 Specific BiCAR-NK/T Cells on Patients With Malignant Tumor

Immunotherapy has become the major breakthrough and the most promising treatment, with the host of development of tumor biology, molecular biology and immunology. ROBO1 is a potential target and spectacular paradigm in the diagnosis and treatment of solid tumors. This study is for evaluation of the safety and efficacy of ROBO1 CAR-NK/T cell immunotherapy for malignant tumors.

Start Date01 May 2019

Sponsor / Collaborator

Asclepius Technology Company Group (Suzhou) Co., Ltd.

NCT03941457

/ Unknown statusPhase 1/2

Clinical Research of ROBO1 Specific BiCAR-NK Cells on Patients With Pancreatic Cancer

Immunotherapy has become the major breakthrough and the most promising treatment, with the host of development of tumor biology, molecular biology and immunology. ROBO1 is a potential target and spectacular paradigm in the treatment of solid tumors. This study is for evaluation of the safety and efficacy of ROBO1 CAR-NK cell immunotherapy for pancreatic cancer.

Start Date01 May 2019

Sponsor / Collaborator

Asclepius (Hangzhou) Medical Technology Co., Ltd.

100 Clinical Results associated with ROBO1

100 Translational Medicine associated with ROBO1

0 Patents (Medical) associated with ROBO1

729

Literatures (Medical) associated with ROBO1

01 Mar 2025·Gene

Incidence of alternative splicing associated with sex and opioid effects in the axon guidance pathway

Article

Author: Sunderland, Gloria R ; Bhamidi, Sreelaya ; Gomez, Andrea N ; Southey, Bruce R ; Rodriguez-Zas, Sandra L

The alternative splicing of a gene results in distinct transcript isoforms that can result in proteins that differ in function. Alternative splicing processes are prevalent in the brain, have varying incidence across brain regions, and can present sexual dimorphism. Exposure to opiates and other substances of abuse can also alter the type and incidence of the splicing process and the relative abundance of the isoforms produced. The disruption of alternative splicing patterns associated with sex differences and morphine exposure in the prefrontal cortex of a pig model was studied. The numbers of genes presenting one or more significant (FDR-adjusted p-value < 0.05) alternative splicing events were 933 and 1,368 genes when comparing females relative to males and morphine- relative to saline-treated animals, respectively. The sex-dependent opioid effect was most extreme in the contrast between morphine- versus saline-treated males with 1,934 significantly differentially spliced genes. The most frequent and significant alternative splicing type was skipped exon (∼56 % event), followed by retained intron (∼15 % events). The pathways encompassing a significant number of differentially spliced genes included axon guidance, glutamatergic synapses, circadian rhythm, and lysine degradation. Genes in these pathways included ROBO1, SEMA6C, GRIN3A, GRM2, ARNTL, CLOCK, HYKK, and DOT1L. Transcription factors ETV7 and DMAP1 presented a significant number of differentially spliced target genes. The distribution of the genes presenting differential alternative splicing in the axon guidance and circadian rhythm pathways indicates that this regulatory mechanism impacts hubs and peripheral genes. The identification of sexual dimorphism in the effect of morphine across multiple pathways confirms the necessity to explore the effects of drugs of abuse within sex. Altogether, our findings advance the understanding of the response to factors that can impact the activity of excitatory synapses by modulating transcriptional mechanisms that support the plasticity of the prefrontal cortex.

01 Jan 2025·Phytomedicine

Sarsasapogenin stimulates angiogenesis and osteogenesis coupling to treat estrogen deficiency-induced osteoporosis by activating the GPX4/SLIT3/ROBO1 axis

Article

Author: Lin, Bingfeng ; Wang, Xuchen ; Xiao, Wenlong ; Wang, Nani ; Zhang, Fanxuan ; Wang, Fang

BACKGROUNDPromoting the coupling of osteogenesis and angiogenesis is a crucial strategy for the treatment of postmenopausal osteoporosis (PMOP). Estrogen deficiency induces ferroptosis, which is closely associated with the pathophysiology of PMOP. Sarsasapogenin (SAR) is a natural sapogenin with anti-oxidative effects. However, it is unclear whether SAR has a protective role against the impaired osteogenesis and angiogenesis coupling in PMOP. In this study, we evaluated the efficacy of SAR in estrogen deficiency-induced osteoporosis and explored the underlying mechanisms.METHODSBone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) were utilized to assess the in vitro effects of SAR on the coupling of osteogenesis and angiogenesis. In vivo experiments involved bilateral ovariectomy (OVX)-induced osteoporosis in mice and glutathione peroxidase 4 (GPX4)-knockout (KO) mice. Mice were orally administered SAR (5 or 10 mg/kg/d) for a duration of 12 weeks. The direct target of SAR was investigated through molecular docking, a cellular thermal shift assay, and surface plasmon resonance. Additionally, RNA sequencing was employed to elucidate the underlying mechanisms.RESULTSSAR treatment improved cell viability and osteogenic differentiation while inhibiting ferroptosis in iron dextran-induced BMSCs. Furthermore, SAR enhanced the production of slit guidance ligand 3 (SLIT3) in these cells, which stimulated angiogenesis by activating its receptor, roundabout human homolog 1 (ROBO1), in HUVECs. An in vitro model of ferroptosis induced by erastin demonstrated that SAR promoted the coupling of osteogenesis and angiogenesis by upregulating the BMSCs-SLIT3/HUVECs-ROBO1 axis. Activation of GPX4 was identified as a contributing factor to the effects of SAR on this coupling. Transfection of GPX4 small interfering RNA (siRNA) in BMSCs negated the impact of SAR on the BMSCs-SLIT3/HUVECs-ROBO1 axis. Additionally, SAR was found to directly interact with GPX4, enhancing protein stability, with an equilibrium dissociation constant of 44.6 μM. Notably, SAR did not increase SLIT3, ROBO1, or indicators of osteogenesis or angiogenesis in GPX4-KO mice.CONCLUSIONSThese findings underscore the significance of restoring the GPX4/SLIT3/ROBO1 axis in promoting the coupling of angiogenesis and osteogenesis. SAR mitigates PMOP, in part, by activating the BMSCs-SLIT3/HUVECs-ROBO1 axis, with GPX4 serving as an upstream signaling modulator responsible for SLIT3 production. Our observations provide experimental evidence supporting the clinical application of SAR in the treatment of PMOP.

31 Dec 2024·Annals of Pediatric Endocrinology & Metabolism

Clinical and genetic features of childhood-onset congenital combined pituitary hormone deficiency: a retrospective, single-center cohort study

Article

Author: Lee, Young Ah ; Shin, Choong Ho ; Ko, Jung Min ; Lee, Yun Jeong ; Lee, Yoonha

Purpose: To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients.Methods: We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing.Results: Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%).Conclusion: Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.

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