CtBP2 promotes proliferation and reduces drug sensitivity in non-small cell lung cancer via the Wnt/β-catenin pathway

被引:23
作者
Wang, D. P. [1 ]
Gu, L. L. [1 ]
Xue, Q. [2 ]
Chen, H. [1 ]
Mao, G. X. [1 ]
机构
[1] Nantong Univ, Dept Oncol, Affiliated Hosp, Nantong 226001, Jiangsu, Peoples R China
[2] Nantong Univ, Dept Thorac Surg, Affiliated Hosp, Nantong 226001, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
CtBP2; NSCLC; Wnt/beta-catenin pathway; proliferation; drug sensitivity; POOR-PROGNOSIS; BETA-CATENIN; CARCINOMA; INVASION; COMPLEX; DVL;
D O I
10.4149/neo_2018_171220N828
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The C-tenninal binding protein 2 (CtBP2) is crucial for the activation of the Wnt/beta-catenin pathway and regulates significant cellular processes in multiple cancer cells. However, the role of CtBP2 in non-small cell lung cancer (NSCLC) remains uncertain. Our western blotting and immunohistochemistry assays revealed that CtBP2 expression was obviously increased in NSCLC tissues and cells. In addition, the chi-square test and Kaplan-Meier analysis showed that over-expression of QBP2 correlates with more invasive tumor phenotype and poor prognosis. In vitro studies with serum starvation-refeeding and CtBP2-shRNA transfection assay demonstrated that CtBP2 expression facilitates NSCLC cell proliferation and reduces sensitivity to cis-diamminedichloroplatinum (CDDP). The possible signaling transduction pathways were investigated, and the immunoprecipitation assay revealed that CtBP2 interacts directly with DvL1. Depletion of CtBP2 resulted in inhibited DvL1 expression and decreased expression of downstream genes. Moreover, our study showed that CtBP2 knockdown enhanced NSCLC cell sensitivity to CDDP through inhibition of the Wnt/beta-catenin pathway. These results suggest that CtBP2 plays a crucial role in NSCLC progression and CDDP sensitivity, and that CtBP2 depletion can provide a new target for NSCLC treatment.
引用
收藏
页码:888 / 897
页数:10
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