Ubiquitin-specific protease 3 promotes cell migration and invasion by interacting with and deubiquitinating SUZ12 in gastric cancer

Journal of Experimental & Clinical Cancer Research

Danping Zhu¹  Li Xiang²  Jianjiao Lin²  Yaying Chen³  Guoxin Li⁴  Wenjing Zhang⁵  Weiyu Dai⁶  Aimin Li⁶  Huiqiong Zhu⁶  Jing Wang⁶  Jiaying Li⁶  Yi Zhang⁶  Yong Sun⁶  Xiaosheng Wu⁶  Yizhi Xiao⁶  Jide Wang⁶  Mengwei Liu⁶  Side Liu⁶  Weimei Tang⁶ 

[1] Department of Clinical Laboratory, General Hospital of Southern Theatre Command;Department of Gastroenterology, Longgang District People’s Hospital;Department of Gastroenterology, The third affiliated Hospital of Guangzhou Medical University;Department of General Surgery, Nanfang Hospital, Southern Medical University;Department of Medical Oncology, the First people’s Hospital of Yunnan Province, Medical School of Kunming University of Science and Technology;Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University;

关键词: USP3;    SUZ12;    Gastric cancer;    EMT;    iTRAQ;   

DOI  :  10.1186/s13046-019-1270-4

来源: DOAJ

【 摘 要 】

Abstract Background The deubiquitinating enzyme ubiquitin-specific protease 3 (USP3) plays a crucial role in numerous biological processes. The aberrant expression of USP3 may have an important role in tumor development. However, the mechanism by which USP3 promotes gastric cancer (GC) metastasis remains largely unknown. Methods Effects of USP3 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated utilizing proteomics, RT-PCR, western blotting, immunohistochemistry, immunofluorescence, cell invasion and migration assays and xenograft tumor models. Results USP3 expression was upregulated in GC compared with matched normal tissues and was predictive of poor survival. USP3 also promoted migration and epithelial-to-mesenchymal transition (EMT) in GC cells. Moreover, TGF-β1 induced USP3 expression, and USP3 knockdown inhibited TGF-β1-induced EMT. Furthermore, we utilized Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) to identify differentially expressed proteins in USP3-overexpressing cells compared with control cells. Importantly, we found that SUZ12 is indispensable for USP3-mediated oncogenic activity in GC. We observed that USP3 interacted with and stabilized SUZ12 via deubiquitination. SUZ12 knockdown inhibited USP3-induced migration and invasion, as well as EMT in GC cells. Examination of clinical samples confirmed that USP3 expression was positively correlated with SUZ12 protein expression and that the levels of USP3 or SUZ12 protein were negatively correlated with the levels of E-cadherin protein. Conclusions These findings identify USP3 as a critical regulator. The USP3-SUZ12 axis might promote tumor progression and could be a potential therapeutic candidate for human GC.

【 授权许可】

Unknown