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.
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Acknowledgements
This study was supported by SK Corp. Korea, KOSEF through the Center for Cell Signaling & Drug Discovery Research (CCS & DDR, R15-2006-002) at Ewha Womans University, by KOSEF Grant FPR05A2-480. Kim HJ, Nam YK, Kim YM, Kim HJ and Lim S were supported by the Brain Korea 21 project.
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Kim, H., Kim, Y., Lim, S. et al. Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis. Oncogene 28, 117–127 (2009). https://doi.org/10.1038/onc.2008.364
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DOI: https://doi.org/10.1038/onc.2008.364
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