<p><em>Cadherin-11</em> is inactivated due to promoter methylation and functions in colorectal cancer as a tumour suppressor</p>

Abstract

Background: The cadherin-11 ( CDH11 , OB-cadherin) gene is a member of the cadherin family and is located on chromosome 16q22.1. Previous studies have revealed that cadherins play significant roles in the development of many human malignancies. Increasing evidence has identified CDH11 as a functional tumour suppressor, which is commonly silenced by promoter methylation, but the functions of this gene in colorectal cancer (CRC) have been unclear. Methods: The CDH11 expression in primary CRC tissues and cell lines was investigated by qRT-PCR, RT-PCR and immunohistochemistry. The promoter methylation status of CDH11 was measured by methylation-specific PCR (MSP). Cell proliferation assay, colony formation assay, flow cytometry analysis, wound-healing assay, transwell assay and in vivo experiments were used to investigate the function of CDH11 in CRC. The mechanisms of CDH11 also were explored by western blots. Results: Our study suggests that CDH11 downregulation in CRC due to its promoter methylation and induced cell cycle arrest in G0/G1 phase and apoptosis, suppressing tumor cell proliferation, colony formation, migration and invasion by affecting the NF-kB signaling pathway. Conclusion: Overall, CDH11 may be considered as a functional tumour suppressor gene (TSG) in CRC, CDH11 has the potential to serve as a valuable prognostic marker for colorectal cancer.

Aberrant Methylation of the 16q22.1 Tumor Suppressor Gene CDH11 Promotes Tumorigenesis and Progression of Renal Cell Carcinoma through NF-kB Pathway

“…The CDH11 gene, located in the 16q22.1 region and belonging to the E-cadherin family, is often involved in an important group of cell-cell adhesion molecules that mediate intercellular adhesion by Ca 2+dependent hemophilic interactions [13] . Because cadherins have been widely documented in cancer development [14] , the promoter CpG island hypermethylation-associated silencing of the CDH11 gene, a component of this superfamily, is consistent with the hypothesis that epigenetic inactivation of this gene could be involved in the tumorigenesis and progression of carcinomas. L Li et al [15] found that the CDH11 gene is frequently methylated in a variety of tumor tissues including esophageal squamous cell carcinoma (13/14, 93%), nasopharyngeal carcinoma (17/18, 94%), hepatocellular carcinoma (28/42, 66%), breast carcinoma (11/12, 91%), gastric carcinoma (13/13, 100%), colon carcinoma (10/11, 90%) and other carcinomas.…”

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure

“…Cadherin-11 (CDH11) is an adhesion protein mainly expressed in mesenchymal tissues that regulates the differentiation and function of osteoblasts. CDH11 was identified to participate in multiple BPs including bone formation, cellular signal transduction, tumor invasion, and metastasis (Lee et al, 2007;Li et al, 2012;Langhe et al, 2016;Madarampalli et al, 2019;Yuan et al, 2019a), and also play important roles in developmental and pathogenic mechanisms of heart valve (Zhou et al, 2013;Bowler et al, 2018). A recent study found that CDH11 contributed to inflammation-driven fibrotic remodeling after myocardial infarction (Schroer et al, 2019), which indicated that the increased CDH11 might be involved in the development of HF through inflammatory response.…”

Comprehensive analysis of DNA methylation and gene expression profiles in rectal cancer

“…For instance, Sepulveda et al [36] found that CDH11 had signi cantly increased CpG methylation and decreased expression in gastric cancer. CDH11 was also downregulated in colorectal cancer due to its promoter methylation, which was linked to cell cycle arrest in the G0/G1 phase and apoptosis [37] . Furthermore, the methylation-induced regulation of CDH11 has been found in many other cancers, such as melanoma and bladder cancer [38][39][40] .…”