Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue.
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.
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Lei
L
Ding
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
Liyong
L
Wang
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
Leiming
L
Sui
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
Huanying
H
Zhao
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
Xiaoxue
X
Xu
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Tengyan
T
Li
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Xiaonan
X
Wang
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Wenjing
W
Li
Department of Bioinformatics, Biomedical Engineering Institute of Capital Medical University, Capital Medical University, Beijing, China.
Ping
P
Zhou
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
Lu
L
Kong
D015415:Biomarkers; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D046888:Tissue Array Analysis; D059467:Transcriptome
D015415:Biomarkers; C473255:CLDN7 protein, human; D057167:Claudins; D016023:Integrins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human