Li Li, Tao Xinyi, Li Yandong, Gao Yong, Li Qinchuan
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Department of Medical Experimental Techniques, Jinzhou Medical University, Jinzhou 121001, China.
J Cancer. 2021 Mar 31;12(11):3145-3153. doi: 10.7150/jca.56097. eCollection 2021.
The co-chaperone protein CDC37 (Cell division cycle 37) is well known to regulate multiple protein kinases and involved in tumor progression. However to date, little is known about its analogue CDC37L1 (Cell division cycle 37 like 1) in tumorigenesis. This study aimed to explore the expression and function of CDC37L1 in gastric cancer (GC). The immunohistochemical staining in a tissue microarray showed a weak expression of CDC37L1 in high grade GC tissues compared with low grade tissues. Consistently, data from online database analysis demonstrated that CDC37L1 level was decreased in stage 4 patients and low expression of CDC37L1 indicated a poor prognosis. Functional studies revealed that CDC37L1 could inhibit GC cell proliferation and migration in CCK8, EdU incorporation, colony formation and transwell assays. In the meantime, CDC37L1 also inhibited the tumorigenicity of GC cells in nude mice. Mechanistically, we found that CDC37L1 had an impact on CDK6 protein expression by western blotting. Palbociclib, a specific CDK4/6 inhibitor, was discovered to block the rapid growth phenotype of GC cells induced by CDC37L1 silencing. Taken together, these findings unveiled a tumor-suppressive role of CDC37L1 in GC, and CDK6 may act as a downstream effector in this process.
共伴侣蛋白CDC37（细胞分裂周期37）在调节多种蛋白激酶及参与肿瘤进展方面广为人知。然而，迄今为止，关于其类似物CDC37L1（类细胞分裂周期37 1）在肿瘤发生中的作用却知之甚少。本研究旨在探讨CDC37L1在胃癌（GC）中的表达及功能。组织芯片的免疫组化染色显示，与低级别GC组织相比，高级别GC组织中CDC37L1表达较弱。同样，在线数据库分析数据表明，IV期患者中CDC37L1水平降低，且CDC37L1低表达提示预后不良。功能研究显示，在CCK8、EdU掺入、集落形成和Transwell实验中，CDC37L1可抑制GC细胞增殖和迁移。同时，CDC37L1还可抑制GC细胞在裸鼠中的致瘤性。机制上，我们通过蛋白质印迹法发现CDC37L1对CDK6蛋白表达有影响。发现特异性CDK4/6抑制剂帕博西尼可阻断由CDC37L1沉默诱导的GC细胞快速生长表型。综上所述，这些发现揭示了CDC37L1在GC中的肿瘤抑制作用，且CDK6可能在此过程中作为下游效应分子发挥作用。
