CtBP2 interacts with TGIF to promote the progression of esophageal squamous cell cancer through the Wnt/β-catenin pathway

C-terminal-binding protein 2 (CtBP2), a transcriptional co-repressor, plays a main role in tumorigenesis and in the development of multiple tumors. Transforming growth interacting factor (TGIF) is involved in a number of cellular signal transduction pathways and is related to tumor occurrence and development. In the present study, the proteins interacting with CtBP2 were identified and the mechanisms underlying the biological activity of CtBP2 in esophageal squamous cell carcinoma (ESCC) were investigated. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to search for known proteins interacting with CtBP2, and co-immunoprecipitation (Co-IP) assay was performed to validate the interactions. Reverse transcription-quantitative PCR (RT-qPCR), immunohistochemistry (IHC) and western blot analysis were performed to examine the expression levels of CtBP2 and TGIF in ESCC. The correlation between CtBP2 and TGIF was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) by Pearson's correlation analysis, and the co-localization of CtBP2 with TGIF in the ECA109 cells was identified using immunofluorescence staining. XAV939 treatment, CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) staining, wound healing and Transwell assays were performed to investigate the signaling pathways involved in the biological activity of CtBP2 in ECA109 cells. According to the results obtained from STRING and Co-IP analysis, an interaction between CtBP2 and TGIF was indicated, and these proteins were co-localized in the nucleus. CtBP2 and TGIF mRNA and protein expression levels were robustly and simultaneously increased in both ESCC tissues and cell lines. There was a direct correlation between CtBP2 and TGIF expression levels in ESCC tissues, and both were significantly associated with metastasis and survival. The TGIF and CtBP2 expression levels were significantly increased or decreased simultaneously, in ECA109 cells transfected with LV-CtBP2 or sh-CtBP2, and vice versa. According to the results of CCK-8 assay, EdU staining and Transwell assay, CtBP2 promoted the proliferation, migration and invasion of ECA109 cells through the Wnt/beta-catenin pathway. On the whole, the present study demonstrates that CtBP2 interacts with TGIF and promotes the malignant progression of ESCC through the Wnt/beta-catenin pathway.

Automated summary

This study investigated the mechanisms underlying the biological activity of CtBP2 in esophageal squamous cell carcinoma (ESCC) and demonstrated that CtBP2 interacts with TGIF and promotes the malignant progression of ESCC through the Wnt/beta-catenin pathway.