biostudies-literatureHuang ZMedical Key Professionals Program of Jiangsu ProvinceMinistry of Science and Technology China 973 ProjectNational Science Foundation of ChinaChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaNCI NIH HHSNIH1792-802https://www.ebi.ac.uk/biostudies/studies/S-EPMC4323690biostudies-literatureUnknown136(8)Originally discovered in neuronal guidance, the Slit-Robo pathway is emerging as an important player in human cancers. However, its involvement and mechanism in colorectal cancer (CRC) remains to be elucidated. Here, we report that Slit2 expression is reduced in CRC tissues compared with adjacent noncancerous tissues. Extensive promoter hypermethylation of the Slit2 gene has been observed in CRC cells, which provides a mechanistic explanation for the Slit2 downregulation in CRC. Functional studies showed that Slit2 inhibits CRC cell migration in a Robo-dependent manner. Robo-interacting ubiquitin-specific protease 33 (USP33) is required for the inhibitory function of Slit2 on CRC cell migration by deubiquitinating and stabilizing Robo1. USP33 expression is downregulated in CRC samples, andInternational journal of cancerUSP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migration.PMC432369020110490615810008672010CB5296032013CB9178039113271081071791P30 CA0605532009CB82540281272299RC2011031R01 CA175360R01CA175360Liu JQuan CKong RChen MWen PDu XWu JYFushimi KHuang ZZhang ZHua DZhu LBian ZChen XCheng HZhang BfalseUSP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migration.Originally discovered in neuronal guidance, the Slit-Robo pathway is emerging as an important player in human cancers. However, its involvement and mechanism in colorectal cancer (CRC) remains to be elucidated. Here, we report that Slit2 expression is reduced in CRC tissues compared with adjacent noncancerous tissues. Extensive promoter hypermethylation of the Slit2 gene has been observed in CRC cells, which provides a mechanistic explanation for the Slit2 downregulation in CRC. Functional studies showed that Slit2 inhibits CRC cell migration in a Robo-dependent manner. Robo-interacting ubiquitin-specific protease 33 (USP33) is required for the inhibitory function of Slit2 on CRC cell migration by deubiquitinating and stabilizing Robo1. USP33 expression is downregulated in CRC samples, and2015-01-01T00:00:00Z2015 Apr2025-06-25T03:04:03.566Z2025-06-25T03:04:03.566ZS-EPMC43236902524226310.1002/ijc.29226