Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue

• Published in: Journal of human genetics 2016-08, Vol.61 (8), p.711-720
• Main Authors: Ding, Lei, Wang, Liyong, Sui, Leiming, Zhao, Huanying, Xu, Xiaoxue, Li, Tengyan, Wang, Xiaonan, Li, Wenjing, Zhou, Ping, Kong, Lu
• Format: Article
• Language: English
• Subjects: Biomarkers; Claudins - genetics; Claudins - metabolism; Cluster Analysis; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Computational Biology - methods; Focal Adhesion Kinase 1 - genetics; Focal Adhesion Kinase 1 - metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Integrins - genetics; Integrins - metabolism; Protein Transport; Signal Transduction; Tissue Array Analysis; Transcriptome
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2016.35

The claudin family of proteins is integral to the structure and function of tight junctions. The role of claudin-7 (Cldn-7, CLDN7) in regulating the integrin/focal adhesion kinase (FAK)/ERK signaling pathway remains poorly understood. Therefore, we investigated differences in gene expression, primarily focusing on CLDN7 and integrin/FAK/ERK signaling pathway genes, between colon cancer and adjacent normal tissues. Quantitative real-time reverse transcription-PCR and immunohistochemistry were utilized to verify the results of mRNA and protein expression, respectively. In silico analysis was used to predict co-regulation between Cldn-7 and integrin/FAK/ERK signaling pathway components, and the STRING database was used to analyze protein-protein interaction pairs among these proteins. Meta-analysis of expression microarrays in The Cancer Genome Atlas (TCGA) database was used to identify significant correlations between Cldn-7 and components of predicted genes in the integrin/FAK/ERK signaling pathway. Our results showed marked cancer stage-specific decreases in the protein expression of Cldn-7, Gelsolin, MAPK1 and MAPK3 in colon cancer samples, and the observed changes for all proteins except Cldn-7 were in agreement with changes in the corresponding mRNA levels. Cldn-7 might indirectly regulate MAPK3 via KRT8 due to KRT8 co-expression with MAPK3 or CLDN7. Our bioinformatics methods supported the hypothesis that Cldn-7 does not directly regulate any genes in the integrin/FAK/ERK signaling pathway. These factors may participate in a common network that regulates cancer progression in which the MAPK pathway serves as the central node.