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

Oncogene. 2009 Jan 8;28(1):117-27. doi: 10.1038/onc.2008.364. Epub 2008 Sep 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Movement / genetics
  • Enzyme Activation
  • Gene Silencing
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology*
  • MAP Kinase Kinase 4 / metabolism
  • Melanoma / enzymology*
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Ubiquitin carboxyl-Terminal Hydrolase L-1, human
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Ubiquitin Thiolesterase