UCH-L1 promotes invasion of breast cancer cells through activating Akt signaling pathway

Yanhong Luo, Jianfeng He, Chunlin Yang, Matthew Orange, Xingcong Ren, Nick Blair, Tao Tan, Jin Ming Yang, Hua Zhu

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

As a de-ubiquitin enzyme, ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to be overexpressed in several human cancers. However, the function of UCH-L1 in invasion of breast cancers is still unclear. Here we report that the expression of UCH-L1 is significantly higher in cancer cells with higher invasive ability. While ectopic UCH-L1 expression failed to alter cell proliferation in MCF-7 cells, it caused a significant upregulation of cellular invasion. Furthermore, siRNA mediated knockdown of UCH-L1 led to suppression of invasion in UCH-L1 overexpressing MCF-7 cells. In order to identify molecular mechanisms underlying these observations, a novel in vitro proximity-dependent biotin identification method was developed by fusing UCH-L1 protein with a bacterial biotin ligase (Escherichia coli BirA R118G, BioID). Streptavidin magnetic beads pulldown assay revealed that UCH-L1 can interact with Akt in MCF-7 cells. Pulldown assay with His tagged recombinant UCH-L1 protein and cell lysate from MCF-7 cells further demonstrated that UCH-L1 preferentially binds to Akt2 for Akt activation. Finally, we demonstrated that overexpression of UCH-L1 led to activation of Akt as evidenced by upregulation of phosphorylated Akt. Thus, these findings demonstrated that UCH-L1 promotes invasion of breast cancer cells and might serve as a potential therapeutic target for treatment of human patients with breast cancers.

Original languageEnglish (US)
Pages (from-to)691-700
Number of pages10
JournalJournal of cellular biochemistry
Volume119
Issue number1
DOIs
StatePublished - Jan 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Luo, Y., He, J., Yang, C., Orange, M., Ren, X., Blair, N., Tan, T., Yang, J. M., & Zhu, H. (2018). UCH-L1 promotes invasion of breast cancer cells through activating Akt signaling pathway. Journal of cellular biochemistry, 119(1), 691-700. https://doi.org/10.1002/jcb.26232