USP11 promotes growth and metastasis of colorectal cancer via PPP1CA-mediated activation of ERK/MAPK signaling pathway.
作者： Hongze Sun , Baochi Ou , Senlin Zhao , Xueni Liu , Liwei Song
DOI: 10.1016/J.EBIOM.2019.08.061
关键词: Colorectal cancer 、 Cancer research 、 Oncogene 、 MAPK/ERK pathway 、 Blot 、 Signal transduction 、 Tumor progression 、 Metastasis 、 Gene knockdown 、 Biology
摘要: Abstract Background USP11 is an ubiquitin-specific protease that plays important role in tumor progression via different mechanisms. However, the expression and prognostic significance of colorectal cancer (CRC) remain unknown. Methods Bioinformatics analyses, qRT-PCR, western blotting, immunohistochemistry were applied for investigating CRC tissues. Kaplan–Meier analysis with log-rank test was used survival analyses. LC–MS/MS performed identifying potential protein interactions USP11. In vitro vivo assays exploring function during CRC. Findings overexpressed tissues functioned as oncogene. Overexpression or knockdown promoted inhibited, respectively, growth metastasis cells vivo. Mechanically, stabilized PPP1CA by deubiquitinating protecting it from proteasome-mediated degradation. Moreover, USP11/PPP1CA complex activating ERK/MAPK signaling pathway. Interpretation pathway stabilizing PPP1CA, suggesting a marker. Fund This work supported National Natural Science Foundation China (NSFC81530044, NSFC81220108021, NSFC81802343), Technology Major Project Grants 2017ZX10203206, Shanghai Sailing Program (19YF1409600) The project Jiaotong University (YG2017QN30).
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