Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer

Zhong, Xian; Zhu, Yaping; Mao, Jianshan; Zhang, Jiawei; Zheng, Shu

doi:10.1007/s00432-012-1353-5

Cited by 41 publications

(35 citation statements)

References 24 publications

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“…PCDH10, a member of nonclustered protocadherin subfamily, was proposed as a tumor suppressor (6)(7)(8) in multiple cancers. Inactivation of PCDH10 because of promoter CpG hypermethylation has been detected in gastric, hepatocellular, colorectal, breast, cervical, lung, nasopharyngeal, esophageal, pancreatic, and bladder cancer (6,(9)(10)(11)(12)(13)(14)(15)(16). Functional studies revealed that re-expression of PCDH10 inhibits cell growth, reduces clonogenicity, restrains cell invasion, and induces cell apoptosis, substantiating its tumor suppressor roles (10,13,14,16).…”

Section: Introductionmentioning

confidence: 87%

A Novel Wnt Regulatory Axis in Endometrioid Endometrial Cancer

et al. 2014

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The Protocadherin 10 (PCDH10) is inactivated often by promoter hypermethylation in various human tumors, but its possible functional role as a tumor suppressor gene is not established. In this study, we identify PCDH10 as a novel Wnt pathway regulatory element in endometrioid endometrial carcinoma (EEC). PCDH10 was downregulated in EEC tumor cells by aberrant methylation of its promoter. Restoring PCDH10 levels suppressed cell growth and triggered apoptosis in EEC cells and tumor xenografts. Gene expression profiling revealed as part of the transcriptomic changes induced by PCDH10 a reduction in levels of MALAT1, a long noncoding RNA, that mediated tumor suppression functions of PCDH10 in EEC cells. We found that MALAT1 transcription was regulated by Wnt/b-catenin signaling via TCF promoter binding and PCDH10 decreased MALAT1 by modulating this pathway. Clinically, MALAT1 expression was associated with multiple parameters in patients with EEC. Taken together, our findings establish a novel PCDH10-Wnt/b-catenin-MALAT1 regulatory axis that contributes to EEC development. Cancer Res; 74(18); 5103-17. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 87%

A Novel Wnt Regulatory Axis in Endometrioid Endometrial Cancer

et al. 2014

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“…The human PCDH10 gene is located at 4q28.3 and is involved as a tumor-suppressor gene. The promoter methylation and downregulation of PCDH10 gene expression has been demonstrated in various human cancer types including lymphoma, as well as gastric, prostate, bladder, colorectal and cervical cancer (9)(10)(11)(12). In previous studies, we found that PCDH10 is broadly expressed in normal adults, but almost undetectable in ΜΜ tissues and cell lines due to the promoter methylation of PCDH10.…”

Section: Introductionmentioning

confidence: 76%

PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway

Zhou

Yuan

et al. 2015

Oncology Reports

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Abstract. The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.

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“…The present study demonstrated that PCDH10 may suppress cell proliferation and invasion in colorectal cancer RKO cells. Flow cytometry analysis of PCDH10-re-expressed RKO cells revealed a significant decrease in the number of cells in the G2/M phase, and an increase in the number of cells in the G0/G1 phase, without inducing apoptosis (11). The ectopic expression of PCDH10 significantly reduced the colony formation efficiencies of the HCT116 cell line in monolayer culture and soft-agar assays in vitro (18) and suppressed tumorigenesis and liver metastasis in vivo, resulting in prolonged mice survival (36).…”

Section: Role Of Pcdh10 As a Functional Tsg In Crcmentioning

confidence: 98%

“…Previously, frequent epigenetic silencing of protocadherin 10 (PCDH10) was revealed in colorectal carcinogenesis. PCDH10 has been proposed to be a tumor suppressor gene involved in the processes of growth control, cell invasion and metastasis (11). The present study focuses on previous findings and aims to review the epigenetic alteration of PCDH10 and the possibility of PCDH10 methylation being a biomarker for CRC diagnosis.…”

Section: Introductionmentioning

confidence: 94%

“…Ying et al (18) demonstrated that the transcriptional silencing of PCDH10 may be reversed by pharmacologic demethylation with 5-aza-2'-deoxycytidine or genetic demethylation with double knockout of DNA methyltransferase (DNMT)1 and DNMT3B in the colorectal cancer HCT116 cell line, suggesting a direct epigenetic mechanism (18). The aberrant methylation of the PCDH10 promoter was also observed in 43-85% of colorectal cancer tissues in several studies, indicating that PCDH10 methylation is a frequent event in colorectal carcinogenesis (11,35,39). In the present study, PCDH10 methylation was detected in colorectal cancer samples, but not in paired adjacent colorectal tissues, in accordance with the study by Yu et al (35), suggesting that the aberrant promoter methylation of PCDH10 is specific to colorectal cancer cells.…”

Section: Aberrant Promoter Methylation and Inactivation Of Pcdh10 In Crcmentioning

confidence: 99%

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Epigenetic silencing of protocadherin 10 in colorectal cancer

et al. 2017

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Abstract. Colorectal cancer (CRC) is one of the most common types of malignant tumor in the world and occurs through a multi-step process resulting from the accumulation of genetic and epigenetic alterations of the genome. Although the molecular mechanisms of the pathogenesis of CRC remain unclear, the inactivation of tumor suppressor genes (TSGs) through promoter methylation serves an important role. Aberrant methylation is a well-defined marker of CRC. At present, the epigenetic silencing of protocadherin 10 (PCDH10) has been identified as an important TSG with key roles in colorectal carcinogenesis, invasion and metastasis as a frequent and early event. Advances in gene methylation detection in tumor tissues and body fluids have led to the development of non-invasive screening methods for CRC. The present study aimed to review the epigenetic alteration of PCDH10 in CRC development, and the potential of PCDH10 to be a non-invasive biomarker for CRC.

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Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer

Cited by 41 publications

References 24 publications

A Novel Wnt Regulatory Axis in Endometrioid Endometrial Cancer

A Novel Wnt Regulatory Axis in Endometrioid Endometrial Cancer

PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway

Epigenetic silencing of protocadherin 10 in colorectal cancer

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