1. USP11 promotes growth and metastasis of colorectal cancer via PPP1CA-mediated activation of ERK/MAPK signaling pathway
- Author
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Xueni Liu, Rangrang Wang, Hongze Sun, Baochi Ou, Zhihai Peng, Liwei Song, Xisheng Liu, and Senlin Zhao
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Male ,Research paper ,Colorectal cancer ,MAP Kinase Signaling System ,Kaplan-Meier Estimate ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,Protein Phosphatase 1 ,medicine ,Animals ,Humans ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Gene knockdown ,Oncogene ,Gene Expression Profiling ,MAPK pathway ,General Medicine ,Middle Aged ,USP11 ,medicine.disease ,Prognosis ,Immunohistochemistry ,PPP1CA ,Blot ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,030104 developmental biology ,Tumor progression ,030220 oncology & carcinogenesis ,Proteolysis ,Cancer research ,Female ,Deubiquitination ,Thiolester Hydrolases ,Signal transduction ,Colorectal Neoplasms ,Transcriptome ,Protein Binding - Abstract
Background USP11 is an ubiquitin-specific protease that plays an important role in tumor progression via different mechanisms. However, the expression and prognostic significance of USP11 in colorectal cancer (CRC) remain unknown. Methods Bioinformatics analyses, qRT-PCR, western blotting, and immunohistochemistry were applied for investigating USP11 expression in CRC tissues. Kaplan–Meier analysis with log-rank test was used for survival analyses. LC–MS/MS was performed for identifying potential protein interactions with USP11. In vitro and in vivo assays were used for exploring the function of USP11 during the progression of CRC. Findings USP11 was overexpressed in CRC tissues and functioned as an oncogene. Overexpression or knockdown of USP11 promoted or inhibited, respectively, the growth and metastasis of CRC cells in vitro and in vivo. Mechanically, USP11 stabilized PPP1CA by deubiquitinating and protecting it from proteasome-mediated degradation. Moreover, the USP11/PPP1CA complex promoted CRC progression by activating the ERK/MAPK signaling pathway. Interpretation USP11 promoted tumor growth and metastasis in CRC via the ERK/MAPK pathway by stabilizing PPP1CA, suggesting USP11 is a potential prognostic marker. Fund This work was supported by National Natural Science Foundation of China (NSFC81530044, NSFC81220108021, NSFC81802343), Technology Major Project of China Grants 2017ZX10203206, Shanghai Sailing Program (19YF1409600) and The project of Shanghai Jiaotong University (YG2017QN30).
- Published
- 2019