Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue
Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue
复制标题
Claudin-7间接调控人结肠癌组织中整合素/FAK信号通路
DOI：
10.1038/jhg.2016.35
复制
发表时间：
2016-08-01
影响因子：
3.5
通讯作者：
Kong, Lu
中科院分区：
文献类型：
--
作者：
Ding, Lei;Wang, Liyong;Kong, Lu
紧密连接蛋白家族是紧密连接结构和功能不可或缺的一部分。 Claudin-7（Cldn-7、CLDN7）在调节整合素/粘着斑激酶 (FAK)/ERK 信号通路中的作用仍知之甚少。因此，我们研究了结肠癌和邻近正常组织之间基因表达的差异，主要关注 CLDN7 和整合素/FAK/ERK 信号通路基因。采用实时定量逆转录-PCR和免疫组织化学分别验证mRNA和蛋白表达的结果。计算机分析用于预测 Cldn-7 和整合素/FAK/ERK 信号通路成分之间的共同调节，STRING 数据库用于分析这些蛋白质之间的蛋白质-蛋白质相互作用对。使用癌症基因组图谱 (TCGA) 数据库中表达微阵列的荟萃分析来确定 Cldn-7 与整合素/FAK/ERK 信号通路中预测基因的组成部分之间的显着相关性。我们的结果显示，结肠癌样本中 Cldn-7、凝溶胶蛋白、MAPK1 和 MAPK3 的蛋白表达显着降低，并且观察到的除 Cldn-7 之外的所有蛋白的变化与相应 mRNA 水平的变化一致。由于 KRT8 与 MAPK3 或 CLDN7 共表达，Cldn-7 可能通过 KRT8 间接调节 MAPK3。我们的生物信息学方法支持这样的假设：Cldn-7 不直接调节整合素/FAK/ERK 信号通路中的任何基因。这些因素可能参与调节癌症进展的共同网络，其中 MAPK 通路作为中心节点。
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.