Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis


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.

DOI: 10.1038/onc.2008.364

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@article{Kim2009UbiquitinCH, title={Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis}, author={H J Kim and Y . M . Kim and Sung-Kil Lim and Yoon Kwon Nam and J H Jeong and K G Lee}, journal={Oncogene}, year={2009}, volume={28}, pages={117-127} }