Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Oncol Rep. 2019 Jul;42(1):67-78. doi: 10.3892/or.2019.7142. Epub 2019 May 2.
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.
羧基末端结合蛋白 1（CtBP1）在许多类型的实体瘤中过表达，并已被发现与癌细胞的增殖、迁移、侵袭和耐药性功能相关。然而，其在肺腺癌中的表达模式和功能尚不清楚。在本研究中，我们观察到 CtBP1 在伴有淋巴结转移的肺腺癌组织中表达上调，并且其过表达与肿瘤分化、大小和总体生存不良相关。通过 MTT 检测和 Transwell 检测分别观察到 shRNA 转染沉默 CtBP1 可抑制 A459 肺腺癌细胞的增殖、迁移和侵袭。使用肺患者来源的肿瘤异种移植（PDTX）小鼠模型的体内研究表明 CtBP1 表达参与肺腺癌的生长，进一步的共免疫沉淀和耗竭实验表明 CtBP1 通过与 SOX2 相互作用调节肺腺癌细胞的生物学行为。CtBP1 和 SOX2 表达均升高的患者的总生存率明显短于这两种转录物表达降低的患者，或 CtBP1 和 SOX2 表达均升高的患者（两者均 P<0.01）。总之，这些发现表明 CtBP1 在肺腺癌中发挥重要作用，并且与 SOX2 一起，可能成为肺腺癌有前途的预后标志物和治疗靶点。
