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

H. J. Kim, Young-Mee Kim, S. Lim, Y. K. Nam, J. Jeong, H. J. Kim, K. J. Lee

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalOncogene
Volume28
Issue number1
DOIs
StatePublished - Jan 8 2009

Fingerprint

Ubiquitin Thiolesterase
Neoplasm Metastasis
Neoplasms
JNK Mitogen-Activated Protein Kinases
Ubiquitin
RNA Interference
Mitogen-Activated Protein Kinases
Cell Adhesion
Amides
Lung Neoplasms
Carcinogenesis
Esters
Hydrolysis

Keywords

  • Akt activation
  • Deubiquitinating enzyme
  • Lung cancer
  • Metastasis
  • Proteomics
  • Tumor invasion
  • UCH-L1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kim, H. J., Kim, Y-M., Lim, S., Nam, Y. K., Jeong, J., Kim, H. J., & Lee, K. J. (2009). Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis. Oncogene, 28(1), 117-127. https://doi.org/10.1038/onc.2008.364

Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis. / Kim, H. J.; Kim, Young-Mee; Lim, S.; Nam, Y. K.; Jeong, J.; Kim, H. J.; Lee, K. J.

In: Oncogene, Vol. 28, No. 1, 08.01.2009, p. 117-127.

Research output: Contribution to journalArticle

Kim, HJ, Kim, Y-M, Lim, S, Nam, YK, Jeong, J, Kim, HJ & Lee, KJ 2009, 'Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis', Oncogene, vol. 28, no. 1, pp. 117-127. https://doi.org/10.1038/onc.2008.364
Kim, H. J. ; Kim, Young-Mee ; Lim, S. ; Nam, Y. K. ; Jeong, J. ; Kim, H. J. ; Lee, K. J. / Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis. In: Oncogene. 2009 ; Vol. 28, No. 1. pp. 117-127.
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