Abstract
Ubiquitin C-terminal hydrolase-L1 (UCH-L1) catalyses the hydrolysis of ubiquitin ester and amide mainly in neuronal cells. Recently it was proposed as a marker with a potential role in carcinogenesis. However, the molecular mechanism underlying the biological function of UCH-L1 in tumor cells is poorly understood. We found that UCH-L1 is highly expressed in non-small lung cancer cell line H157, having high invasive potential, and that the expression of UCH-L1 in tumor cells enhances their invasive potential in vitro and in vivo. UCH-L1 changes cell morphology by regulating cell adhesion through Akt-mediated pathway. Suppressing UCH-L1 expression by RNAi significantly suppressed the invasion in vitro and in vivo, and the activation of Akt and downstream mitogen activated protein kinases c-Jun N-terminal kinases and p38, but not ERK. In Akt-negative mutants, overexpression of UCH-L1 does not affect the invasion and migration capability of H157 cells. These results suggest that UCH-L1 is a key molecule to regulate tumor-cell invasion by upstream activation of Akt.
Original language | English (US) |
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Pages (from-to) | 117-127 |
Number of pages | 11 |
Journal | Oncogene |
Volume | 28 |
Issue number | 1 |
DOIs | |
State | Published - Jan 8 2009 |
Externally published | Yes |
Keywords
- Akt activation
- Deubiquitinating enzyme
- Lung cancer
- Metastasis
- Proteomics
- Tumor invasion
- UCH-L1
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research