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Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue
Lei Ding1, Liyong Wang2, Leiming Sui2
1Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Abstract:
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.
Insights
Claudin-7 (CLDN7) protein expression decreases in colon cancer, potentially impacting the MAPK pathway. While not directly regulating it, CLDN7 may indirectly influence cancer progression through interactions with other signaling molecules.
Area of Science:
- Molecular biology
- Cancer research
- Cellular signaling
Background:
- Tight junctions are crucial for cellular integrity, involving the claudin protein family.
- The specific role of claudin-7 (CLDN7) in the integrin/focal adhesion kinase (FAK)/ERK signaling pathway is not well-defined.
- Understanding CLDN7's function is key to exploring colon cancer mechanisms.
Purpose of the Study:
- To investigate differential gene expression of CLDN7 and the integrin/FAK/ERK pathway in colon cancer versus normal tissues.
- To elucidate the relationship between CLDN7 and key signaling pathway components.
- To explore potential regulatory networks in colon cancer progression.
Main Methods:
- Quantitative real-time reverse transcription-PCR for mRNA expression analysis.
- Immunohistochemistry for protein expression validation.
- In silico analysis, STRING database, and TCGA meta-analysis for gene co-regulation and protein interactions.
Main Results:
- Significant, stage-specific decreases in protein expression of CLDN7, Gelsolin, MAPK1, and MAPK3 were observed in colon cancer.
- mRNA levels generally correlated with protein changes, except for CLDN7.
- Bioinformatics suggested CLDN7 does not directly regulate the integrin/FAK/ERK pathway but may indirectly affect MAPK3 via KRT8.
Conclusions:
- CLDN7 protein levels are altered in colon cancer, with potential indirect roles in pathway regulation.
- The MAPK pathway may act as a central node in a network regulating colon cancer progression.
- Further research into CLDN7's interactions is warranted to understand its role in cancer.
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