Expression changes of cell-cell adhesion-related genes in colorectal tumors

Abstract

Abstract. Epithelial tissues achieve a highly organized structure due to cell-cell junction complexes. Carcinogenesis is accompanied by changes in cell interactions and tissue morphology, which appear in the early stages of benign tumors and progress along with invasive potential. The aim of the present study was to analyze the changes in expression levels of genes encoding intercellular junction proteins that have been previously identified to be differentially expressed in colorectal tumors compared with normal mucosa samples (fold change, >2.5) in genome-wide expression profiling. The expression of 20 selected genes was assessed using quantitative reverse transcription polymerase chain reaction in 26 colorectal cancer, 42 adenoma and 24 normal mucosa samples. Between these tissue types, differences were observed in the mRNA levels of genes encoding adherens junction proteins (upregulation of CDH3 and CDH11, and downregulation of CDH19 and PTPRF), tight junction proteins (upregulation of CLDN1 and CLDN2, and downregulation of CLDN5, CLDN8, CLDN23, CLDN15, JAM2 and CGN) and desmosomes (upregulation of DSC3 and DSG3, and downregulation of DSC2), in addition to a decrease in the expression of certain other genes involved in intercellular connections: PCDHB14, PCDH7, MUPCDH and NEO1. The differences between tissue types were statistically significant, and separate clustering of normal adenoma and carcinoma samples was observed in a hierarchical clustering analysis. These results indicate that the morphological changes in neoplastic colon tissue that occur during the 'adenoma-carcinoma sequence' are accompanied by specific changes in the expression of multiple genes encoding the majority of cell-cell junction complexes. The particular differential expression patterns appear to be consistent among patients with cancer and adenoma, in addition to normal mucosa samples.

CDH11 inhibits proliferation and invasion in head and neck cancer

“…Consistent with an oncogenic role, CDH11, promotes invasion of prostate cancer cells and metastasis to bone (5,20). CDH11 expression is upregulated in colorectal tumors (24). In oral squamous cell carcinoma, a previous immunohistochemical study showed that CDH11 is overexpressed but did not perform functional studies (25).…”

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

“…Claudins have also been suggested to have an important role in carcinogenesis. Bujko et al . firstly demonstrated that the concomitant decrease of CLDN5 and CLDN15 levels were associated with CRC development.…”

Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers

“…Methylation of the RET promoter CpG island is associated with poor CRC prognosis [22]. Lower expression of the tight junction protein-encoding gene JAM2 has been observed in colon tumors compared with normal specimens [23]. In a mouse genome-wide association study, GSG1L regulates glutamate receptor activity and was among the genes associated with a chromosome 15 colorectal cancer genetic susceptibility locus [24].…”