Lysyl oxidase like 4, a novel target gene of TGF-β1 signaling, can negatively regulate TGF-β1-induced cell motility in PLC/PRF/5 hepatoma cells

Dong Joon Kim, Dong Chul Lee, Suk Jin Yang, Jung Ju Lee, Eun Mi Bae, Dong Min Kim, Sang Hyun Min, Soo Jung Kim, Dong Chul Kang, Byung Chan Sang, Pyung Keun Myung, Kyung Chan Park, Young Il Yeom

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Transforming growth factor-β1 (TGF-β1) is a multi-functional cytokine involved in the regulation of cell proliferation, differentiation and extracellular matrix formation. In search for novel genes mediating the TGF-β1 function at downstream signaling, we performed a cDNA microarray analysis and identified 60 genes whose expression is regulated by TGF-β1 in the liver cancer cell line PLC/PRF/5. Among them, we report here lysyl oxidase like 4 (LOXL4) as a novel target of TGF-β1 signaling, and provide experimental evidence for its expression regulation and function. LOXL4 was found to be the only member of LOX family whose expression is induced by TGF-β1 in hepatoma cells. Deletion mapping of the LOXL4 promoter indicated that the TGF-β1 regulation of LOXL4 expression is mediated through the binding of AP1 transcription factor to a conserved region of the promoter. This was confirmed by the chromatin immunoprecipitation assay that captured c-Fos-bound chromatin from TGF-β1-treated cells. Forced expression of LOXL4 in PLC/PRF/5 cells resulted in inhibition of cell motility through Matrigel in the presence of TGF-β1 treatment. In parallel, LOXL4 suppressed the expression of laminins and α3 integrin and the activity of MMP2. These results suggest that LOXL4 may function as a negative feedback regulator of TGF-β1 in cell invasion by inhibiting the metabolism of extracellular matrix (ECM) components.

Original languageEnglish (US)
Pages (from-to)521-527
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume373
Issue number4
DOIs
StatePublished - Sep 5 2008

Keywords

  • Invasion
  • LOXL4
  • MMP2
  • TGF-β1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kim, D. J., Lee, D. C., Yang, S. J., Lee, J. J., Bae, E. M., Kim, D. M., Min, S. H., Kim, S. J., Kang, D. C., Sang, B. C., Myung, P. K., Park, K. C., & Yeom, Y. I. (2008). Lysyl oxidase like 4, a novel target gene of TGF-β1 signaling, can negatively regulate TGF-β1-induced cell motility in PLC/PRF/5 hepatoma cells. Biochemical and Biophysical Research Communications, 373(4), 521-527. https://doi.org/10.1016/j.bbrc.2008.06.071