Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer
Open accessAbstract
Purpose Aberrant DNA methylation is common in cancer cells. Epigenetic alterations resulting in the loss of tumor suppression gene functions are frequently involved in tumor development and progression. Recently, methylation of PCDH10 was reported to be associated with multiple hematologic malignancies as well as some solid tumors. Whether the down-regulation of PCDH10 happens in CRC remains unknown. Methods Methylation status of PCDH10 was evaluated by methylation-specific PCR analysis. The effects of PCDH10 re-expression were determined in growth, colony formation, cell cycle, and invasion assays. Results In this study, we found that 100 % (8 of 8) of colorectal cancer cell lines were silenced for PCDH10, but not normal colorectal epithelial cells. Demethylation treatment confirmed that the reduced expression is associated closely with promoter methylation. Hyper-methylation of PCDH10 was also detected in 85 % of primary colorectal tumors, but not in adjacent normal colorectal tissues. Conclusions Our results suggest that PCDH10 is an important tumor suppression gene with key roles of suppressing cell proliferation, clonogenicity, and inhibiting cell invasion in the development of colorectal cancer. Thus, PCDH10 methylation may constitute a useful biomarker of colorectal cancer patients.
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pcdh10a is expressed by migrating zebrafish neural crest cells and acts as a tumor suppressor in several cancers.
“which is expressed by migrating zebrafish neural crest cells, and acts as a tumor suppressor in several cancers [61]-[63].”
From Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin (2013) · cites this paper as [61]
The Discussion (p. 5) identifies human PCDH10 as a functional tumor-suppression gene in colorectal cancer and discusses findings in other tumors. The paper does not establish that zebrafish pcdh10a is expressed in migrating neural crest cells, or that the zebrafish gene acts as a tumor suppressor. (LLM, conf=0.88)
Experimental — accuracy not yet measuredpcdh10a is included in the co-enrichment list of melanocytes and iridophores.
“Also included is the cell adhesion molecule pcdh10a, which is expressed by migrating zebrafish neural crest cells, and acts as a tumor suppressor in several cancers [61]-[63].”
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Higdon, C. W., Mitra, R. D., & Johnson, S. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067801 · Cited by 125 · see citing works
- Authors
- Zhong, X., Zhu, Y., Mao, J., Zhang, J., & Zheng, S.
- Affiliations
- Second Affiliated Hospital of Zhejiang University (CN)
- Corresponding author
- Zhang, Jiawei
- Venue
- Journal of Cancer Research and Clinical Oncology
- Published
- 2012-11-22
- Volume
- 139
- Issue
- 3
- Pages
- 485-490
- ISSN
- 0084-5353 (ISSN-L)
- 0171-5216
- 1432-1335
- PMC
- PMC11824289
- OpenAlex
- W2007563559
- Cited by
- 76
- References
- 0
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 33 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 5
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Cancer Research and Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- University of Hong Kong
- Zhejiang University
- Chinese University of Hong Kong
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- PCDH10, DNA methylation, colorectal cancer, epigenetic silencing, tumor suppressor, promoter hypermethylation, cell proliferation, clonogenicity, cell invasion, demethylation, tumor markers
- MeSH terms
- Protocadherins, Carcinoma, Gene Frequency, Humans, Neoplasm Invasiveness, Tumor Cells, Cultured, Colorectal Neoplasms, Cadherins, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Caco-2 Cells, HT29 Cells, DNA Methylation, Gene Silencing, HCT116 Cells, Cell Proliferation, Epigenetic Repression
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