Department of Clinical Laboratory, Fuyang Second People's Hospital, Fuyang Infectious Disease Clinical College, Anhui Medical University, Fuyang, 236015, Anhui, China.
Ocean University of China, Qingdao, 266100, Shandong, China.
Clin Transl Oncol. 2023 Mar;25(3):817-829. doi: 10.1007/s12094-022-02993-7. Epub 2022 Nov 23.
Lung squamous cell carcinoma (LUSC) is recognized as the major subtypes of non-small cell lung cancer (NSCLC). Circulating tumor cells (CTCs) are critical players in tumor metastasis. A molecular profiling of CTCs has previously identified notch receptor 1 (Notch1) as an important mediator in NSCLC. Therefore, we investigate Notch1 roles in LUSC and its related mechanisms.
The serum levels of Notch1 were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The CTCs isolated from blood samples were characterized via an immunofluorescence method. Cell motion was determined using Transwell chambers. The regulatory relationship between Notch1 and zinc finger E-box-binding homeobox 1 (ZEB1) was verified by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The protein levels were detected by western blotting.
Higher Notch1 expression in patients with LUSC than that in normal controls was observed. Notch1 knockdown inhibited cell motion and epithelial-mesenchymal transition (EMT). ZEB1 transcriptionally activated Notch1. ZEB1 upregulation exacerbated the malignant phenotypes of CTCs.
ZEB1-activated Notch1 promotes malignant phenotypes of CTCs in LUSC and indicates poor prognosis.
肺鳞状细胞癌（LUSC）被认为是非小细胞肺癌（NSCLC）的主要亚型。循环肿瘤细胞（CTC）是肿瘤转移的关键参与者。先前的 CTC 分子谱分析鉴定出 Notch 受体 1（Notch1）是 NSCLC 的重要介质。因此，我们研究了 Notch1 在 LUSC 中的作用及其相关机制。
通过逆转录定量聚合酶链反应（RT-qPCR）测量 Notch1 的血清水平。通过免疫荧光法对血液样本中分离的 CTC 进行表征。使用 Transwell 室测定细胞运动。通过染色质免疫沉淀（ChIP）和荧光素酶报告基因测定验证 Notch1 和锌指 E 盒结合同源盒 1（ZEB1）之间的调节关系。通过蛋白质印迹检测蛋白水平。
与正常对照组相比，LUSC 患者的 Notch1 表达更高。Notch1 敲低抑制细胞运动和上皮-间充质转化（EMT）。ZEB1 转录激活 Notch1。ZEB1 的上调加剧了 CTC 的恶性表型。
ZEB1 激活的 Notch1 促进了 LUSC 中 CTC 的恶性表型，并预示着不良预后。
