ArticleOncogene2012
Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- DNA methylation profiling identifies long-range epigenetic silencing of clustered protocadherins as a key determinant of meningioma progression.Nature communications · 2026Article
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- Identification of SENP7 and UTF1/VENTX as new loci influencing clustered protocadherin methylation across blood and brain using a genome-wide association study.Molecular psychiatry · 2026Article
- Transient intracellular expression of PD-L1 and VEGFR2 bispecific nanobody in cancer cells inspires long-term T cell activation and infiltration to combat tumor and inhibit cancer metastasis.Molecular cancer · 2025Article
- Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx.International journal of molecular sciences · 2025Article
- CRYβB2 alters cell adhesion to promote invasion in a triple-negative breast cancer cell line.BMC research notes · 2025Article
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- The Role of Protocadherin γ in Adult Sensory Neurons and Skin Reinnervation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Genome-wide analysis toward the epigenetic aetiology of myelodysplastic syndrome disease progression and pharmacoepigenomic basis of hypomethylating agents drug treatment response.Human genomics · 2023Article
- A Unique Role for Protocadherin γC3 in Promoting Dendrite Arborization through an Axin1-Dependent Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Protocadherin gamma C3: a new player in regulating vascular barrier function.Neural regeneration research · 2023Review
- Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells.Clinical epigenetics · 2022Article
- Protocadherin Gamma C3 (PCDHGC3) Is Strongly Expressed in Glioblastoma and Its High Expression Is Associated with Longer Progression-Free Survival of Patients.International journal of molecular sciences · 2022Article
- Comparing Urinary Glycoproteins among Three Urogenital Cancers and Identifying Prostate Cancer-Specific Glycoproteins.ACS omega · 2022Article
- Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Long noncoding RNA SOX2OT promotes pancreatic cancer cell migration and invasion through destabilizing FUS protein via ubiquitination.Cell death discovery · 2021Article
- Advancement and properties of circular RNAs in prostate cancer: An emerging and compelling frontier for discovering.International journal of biological sciences · 2021Review
- Cadherins down-regulation: towards a better understanding of their relevance in colorectal cancer.Histology and histopathology · 2020Review
- Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial CellsFrontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer types. Here we utilize Illumina Beadchip methylation array analysis to identify LRES across 800 kb of chromosome 5q31 in colorectal adenomas and carcinomas (n=34) relative to normal colonic epithelial DNA (n=6). This region encompasses 53 individual protocadherin (PCDH) genes divided among three gene clusters. Hypermethylation within these gene clusters is asynchronous; while most PCDH hypermethylation occurs early, and is apparent in adenomas, PCDHGC3 promoter methylation occurs later in the adenoma-carcinoma transition. PCDHGC3 was hypermethylated in 17/28 carcinomas (60.7%) according to methylation array analysis. Quantitative real-time reverse transcription-polymerase chain reaction showed that PCDHGC3 is the highest expressed PCDH in normal colonic epithelium, and that there was a strong reciprocal relationship between PCDHGC3 methylation and expression in carcinomas (R=-0.84). PCDH LRES patterns are reflected in colorectal tumour cell lines; adenoma cell lines are not methylated at PCDHGC3 and show abundant expression at the mRNA and protein level, while the expression is suppressed in hypermethylated carcinoma cell lines (R=-0.73). Short-interfering RNA-mediated reduction of PCDHGC3 led to a decrease of apoptosis in RG/C2 adenoma cells, and overexpression of PCDHGC3 in HCT116 cells resulted in the reduction of colony formation, consistent with tumour suppressor capabilities for PCDHGC3. Further functional analysis showed that PCDHGC3 can suppress Wnt and mammalian target of rapamycin signalling in colorectal cancer cell lines. Taken together, our data suggest that the PCDH LRES is an important tumour suppressor locus in colorectal cancer, and that PCDHGC3 may be a strong marker and driver for the adenoma-carcinoma transition.
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Registered trials
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