ArticleMolecular oncology2023
Slit2/Robo1 signaling inhibits small-cell lung cancer by targeting β-catenin signaling in tumor cells and macrophages.
Article in Molecular oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- Repression of ROBO1 Enhances Cisplatin Sensitivity in Hypermethylated Subtype of HPV-Positive Head and Neck Carcinoma.Cancer science · 2026Article
- Identification and validation of serum SLIT1 as a biomarker for predicting anti-PD-1/PD-L1 resistance in non-small cell lung cancer.Biological procedures online · 2026Article
- Activation of SLIT2/ROBO1/LRP6 axis aggravates cartilage degradation via β-catenin signaling in TMJOA.JCI insight · 2026Article
- Abnormal levels of miRNA in pancreatic cancer are linked to tumor progression by regulating the translation of tumor-associated mRNA.Annals of medicine · 2025Review
- SLIT2 inhibits lung adenocarcinoma progression by suppressing epithelial-mesenchymal transition.Discover oncology · 2025Article
- Harnessing GSK-3β inhibition for lung cancer therapy: emerging opportunities and challenges.Medical oncology (Northwood, London, England) · 2025Review
- Integration of humanized ROBO1 CAR in PD-1 locus in natural killer cells delivers synergistic tumor-killing effect against non-small cell lung cancer.Cancer gene therapy · 2025Article
- S100A9 enhances tumor immune suppression and cancer cell survival in small cell lung cancer.Cell death & disease · 2025Article
- SLIT2 modulates NMIIA to regulate mitophagy and suppress hepatocellular carcinoma progression.BMC cancer · 2025Article
- Cancer-metastasis-on-a-chip reveals efficacy of bevacizumab and siRNA in overcoming carboplatin resistance in SKOV3 ovarian cancer within a fibrotic metastatic microenvironment.Materials today. Bio · 2025Article
- Polarization of Tumor Cells and Tumor-Associated Macrophages: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors.Journal of translational medicine · 2025Article
- SLIT3-mediated intratumoral crosstalk induces neuroblastoma differentiation via a spontaneous regression-like program.Journal of translational medicine · 2025Article
- Machine learning developed immune-related exosome signature for prognosis and immunotherapy benefit in bladder cancer.Discover oncology · 2025Article
- ROBO1 enhanced esophageal carcinoma cell radioresistance through accelerating G3BP2-mediated eIF3A degradation.Cell death & disease · 2025Article
- Efficacy and mechanism of the XPO1 inhibitor selinexor combined with decitabine in T-cell lymphoblastic lymphoma.Annals of hematology · 2025Article
- The neurorepellent SLIT2 inhibits LPS-induced proinflammatory signaling in macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment.Frontiers in immunology · 2024Review
- The genomic landscape of the immune system in lung cancer: present insights and continuing investigations.Frontiers in genetics · 2024Review
- Alveolar type 2 cells marker geneFrontiers in oncology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 (SLIT2) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue. In addition, the expression of the SLIT2 receptor, roundabout guidance receptor 1 (ROBO1), is upregulated. We find a positive association between SLIT2 expression and the Yes1 associated transcriptional regulator (YAP1)-expressing SCLC subtype (SCLC-Y), which shows a better prognosis. Using genetically engineered SCLC cells, adenovirus gene therapy, and preclinical xenograft models, we show that SLIT2 overexpression or the deletion of ROBO1 restricts tumor growth in vitro and in vivo. Mechanistic studies revealed significant inhibition of myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs) in the SCLC tumors. In addition, SLIT2 enhances M1-like and phagocytic macrophages. Molecular analysis showed that ROBO1 knockout or SLIT2 overexpression suppresses the transforming growth factor beta 1 (TGF-β1)/β-catenin signaling pathway in both tumor cells and macrophages. Overall, we find that SLIT2 and ROBO1 have contrasting effects on SCLC tumors. SLIT2 suppresses, whereas ROBO1 promotes, SCLC growth by regulating the Tgf-β1/glycogen synthase kinase-3 beta (GSK3)/β-catenin signaling pathway in tumor cells and TAMs. These studies indicate that SLIT2 could be used as a novel therapeutic agent against aggressive SCLC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.