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

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Title
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
Author(s)
Dong Joon Kim; Dong Chul Lee; Suk Jin Yang; Jeong Ju Lee; Eun Mi Bae; D M Kim; S H Min; Soo Jung Kim; D C Kang; B C Sang; P K Myung; Kyung Chan ParkYoung Il Yeom
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 373, no. 4, pp. 521-527
Publication Year
2008
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.
Keyword
InvasionLOXL4MMP2TGF-β1
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2008.06.071
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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