CtBP1 interacts with SOX2 to promote the growth, migration and invasion of lung adenocarcinoma.

Abstract

Carboxyl-terminal binding protein 1 (CtBP1) is overexpressed in many types of solid tumors and has been found to be functionally associated with proliferation, migration, invasion and drug resistance of cancer cells. However, its expression pattern and functions in lung adenocarcinoma remain unclear. In the present study, we observed that the expression of CtBP1 was upregulated in the lung adenocarcinoma tissues of patients with lymph node metastasis and that its overexpression was correlated with tumor differentiation, size and poor overall survival. Silencing of CtBP1 by transfection with shRNA inhibited the proliferation, migration and invasion of A459 lung adenocarcinoma cells in vitro as determined by MTT assay and Transwell assay, respectively. In vivo studies using a lung patient-derived tumor xenograft (PDTX) mouse model implicated CtBP1 expression in lung adenocarcinoma growth, and further in vitro co-immunoprecipitation and depletion experiments indicated that CtBP1 regulated the biological behavior of lung adenocarcinoma cells by interacting with SOX2. Patients with elevated expression of both CtBP1 and SOX2 expression had a significantly shorter overall survival rate than patients with reduced expression of these transcripts, or than patients with elevated expression of only one transcript (P<0.01 in both cases). Taken together, these findings suggest that CtBP1 plays an important role in lung adenocarcinoma and, along with SOX2, may serve as a viable prognostic marker and therapeutic target for lung adenocarcinoma.