Xue Wanting, Cai Lihong, Li Su, Hou Yujia, Wang Yan-Dong, Yang Dongbin, Xia Yubing, Nie Xiaobo
Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Basic Medical Sciences, Hebi Key Laboratory of Liver Disease, People's Hospital of Hebi, Henan University, Kaifeng, Hebi, China.
Kaifeng Key Laboratory of Radiation Oncology, Kaifeng Cancer Hospital, Kaifeng University, Kaifeng, 475003, China.
Discov Oncol. 2023 Jul 24;14(1):136. doi: 10.1007/s12672-023-00739-7.
Non-small cell lung cancer (NSCLC) is the malignant tumor with the highest morbidity and leading cause of death worldwide, whereas its pathogenesis has not been fully elucidated. Although mutations in some crucial genes in WNT pathways such as β-catenin and APC are not common in NSCLC, the abnormal signal transduction of WNT pathways is still closely related to the occurrence and progression of NSCLC. WNT ligands (WNTs) are a class of secreted glycoproteins that activate WNT pathways through binding to their receptors and play important regulatory roles in embryonic development, cell differentiation, and tissue regeneration. Therefore, the abnormal expression or dysfunction of WNTs undoubtedly affects WNT pathways and thus participates in the pathogenesis of diseases. There are 19 members of human WNTs, WNT1, WNT2, WNT2b, WNT3, WNT3a, WNT4, WNT5a, WNT5b, WNT6, WNT7a, WNT7b, WNT8a, WNT8b, WNT9a, WNT9b, WNT10a, WNT10b, WNT11 and WNT16. The expression levels of WNTs, binding receptors, and activated WNT pathways are diverse in different tissue types, which endows the complexity of WNT pathways and multifarious biological effects. Although abundant studies have reported the role of WNTs in the pathogenesis of NSCLC, it still needs further study as therapeutic targets for lung cancer. This review will systematically summarize current research on human WNTs in NSCLC, from molecular pathogenesis to potential clinical practice.
非小细胞肺癌（NSCLC）是全球发病率最高且致死率居首的恶性肿瘤，但其发病机制尚未完全阐明。尽管WNT信号通路中一些关键基因（如β-连环蛋白和腺瘤性息肉病基因）的突变在NSCLC中并不常见，但WNT信号通路的异常信号转导仍与NSCLC的发生发展密切相关。WNT配体（WNTs）是一类分泌型糖蛋白，通过与受体结合激活WNT信号通路，并在胚胎发育、细胞分化和组织再生中发挥重要的调节作用。因此，WNTs的异常表达或功能障碍无疑会影响WNT信号通路，进而参与疾病的发病机制。人类WNTs有19个成员，即WNT1、WNT2、WNT2b、WNT3、WNT3a、WNT4、WNT5a、WNT5b、WNT6、WNT7a、WNT7b、WNT8a、WNT8b、WNT9a、WNT9b、WNT10a、WNT10b、WNT11和WNT16。WNTs的表达水平、结合受体以及激活的WNT信号通路在不同组织类型中各不相同，这赋予了WNT信号通路的复杂性和多样的生物学效应。尽管已有大量研究报道了WNTs在NSCLC发病机制中的作用，但作为肺癌的治疗靶点仍需进一步研究。本综述将系统总结目前关于人类WNTs在NSCLC中的研究，从分子发病机制到潜在的临床应用。
