ArticleGastroenterology2007
Epigenetic and genetic alterations in Netrin-1 receptors UNC5C and DCC in human colon cancer.
Article in Gastroenterology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
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- Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling.Cell reports · 2024Article
- Research progress of the netrins and their receptors in cancer.Journal of cellular and molecular medicine · 2024Review
- Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Circulating cell-free DNA methylation patterns as non-invasive biomarkers to monitor colorectal cancer treatment efficacy without referencing primary site mutation profiles.Molecular cancer · 2024Article
- The nerve cells in gastrointestinal cancers: from molecular mechanisms to clinical intervention.Oncogene · 2024Review
- Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration.Cancers · 2023Article
- Inactivation of axon guidance molecule netrin-1 in human colorectal cancer by an epigenetic mechanism.Biochemical and biophysical research communications · 2022Article
- Promoter methylation-mediated repression of UNC5 receptors and the associated clinical significance in human colorectal cancer.Clinical epigenetics · 2021Article
- UNC5A, an epigenetically silenced gene, functions as a tumor suppressor in non-small cell lung cancer.Saudi journal of biological sciences · 2020Article
- Article
- Netrin-1 promotes the collective cell migration of liver cancer cells in a 3D cell culture model.Journal of physiology and biochemistry · 2019Article
- Exosomal Induction of Tumor Innervation.Cancer research · 2019Review
- Significant Pattern of Promoter Hypermethylation of UNC5C Gene in Colorectal Cancer and Its Implication in Late Stage DiseaseAsian Pacific journal of cancer prevention : APJCP · 2018Article
- Integrated analysis highlights APC11 protein expression as a likely new independent predictive marker for colorectal cancer.Scientific reports · 2018Article
- The role ofAnnals of translational medicine · 2018Review
- HypermethylatedAmerican journal of translational research · 2018Article
- Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas.Cancer science · 2018Article
- Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia.PLoS pathogens · 2017Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsDCC and UNC5C, Netrin-1 dependence receptors, perform an important role in intestinal epithelial biology. Both receptors frequently are down-regulated in colorectal cancer (CRC). Although CRCs frequently lose DCC owing to deletions at 18q, the mechanism for the UNC5C loss is poorly understood. We hypothesized that UNC5C is silenced epigenetically in CRC, and that there are interactions between losses of UNC5C and DCC in colorectal tumorigenesis.
methodsGene expression and epigenetic analysis of UNC5C was examined in 8 CRC cell lines, 147 sporadic CRCs with corresponding normal mucosa, and 52 adenomatous polyps (APs). Allelic imbalances at DCC were determined in CRCs. The molecular analyses were compared with genetic and clinicopathologic features.
resultsAll CRC cell lines showed UNC5C methylation and an associated loss of gene expression. Treatment with 5-Aza-2'-deoxycytidine resulted in restoration of gene transcription. UNC5C methylation was significantly higher in CRCs (76.2%) and APs (63.5%) than in corresponding normal mucosa (6%; P < .0001). Allelic imbalance at DCC was observed in 61% of CRCs. Overall, 89.3% of CRCs had alterations of one of the dependence receptors. UNC5C methylation occurred predominantly in the earlier lesions (APs and early CRCs), whereas DCC losses were more often in advanced CRCs.
conclusionsThe majority of CRCs harbor defects in Netrin-1 receptors, emphasizing the importance of this growth regulatory pathway in cancer. Furthermore, the timing of the molecular alterations in the Netrin-1 receptors is not random because UNC5C inactivation occurs early, whereas DCC losses occurs in later stages of multistep colorectal carcinogenesis.
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