Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Neoplasma. 2018 Nov 15;65(6):888-897. doi: 10.4149/neo_2018_171220N828. Epub 2018 Sep 4.
The C-terminal binding protein 2 (CtBP2) is crucial for the activation of the Wnt/β-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 CtBP2 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/β-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.
C 末端结合蛋白 2（CtBP2）对于 Wnt/β-连环蛋白通路的激活至关重要，并调节多种癌细胞中的重要细胞过程。然而，CtBP2 在非小细胞肺癌（NSCLC）中的作用仍不确定。我们的 Western blot 和免疫组织化学检测显示，CtBP2 在 NSCLC 组织和细胞中表达明显增加。此外，卡方检验和 Kaplan-Meier 分析表明，CtBP2 的过表达与侵袭性更强的肿瘤表型和不良预后相关。血清饥饿再喂养和 CtBP2-shRNA 转染实验的体外研究表明，CtBP2 表达促进 NSCLC 细胞增殖，并降低对顺铂（CDDP）的敏感性。我们还研究了可能的信号转导通路，免疫沉淀检测显示 CtBP2 与 DvL1 直接相互作用。CtBP2 的耗竭导致 DvL1 表达抑制和下游基因表达减少。此外，我们的研究表明，CtBP2 敲低通过抑制 Wnt/β-连环蛋白通路增强 NSCLC 细胞对 CDDP 的敏感性。这些结果表明，CtBP2 在 NSCLC 进展和 CDDP 敏感性中起关键作用，CtBP2 的耗竭可为 NSCLC 的治疗提供新的靶点。
