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 Citations (Scopus)

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
Externally publishedYes

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Protein-Lysine 6-Oxidase
Transforming Growth Factors
Programmable logic controllers
Cell Movement
Hepatocellular Carcinoma
Genes
Cells
Chromatin
Extracellular Matrix
Chromatin Immunoprecipitation
Cell proliferation
Laminin
Microarray Analysis
Liver Neoplasms
Microarrays
Oligonucleotide Array Sequence Analysis
Genetic Promoter Regions
Metabolism
Gene expression
Integrins

Keywords

  • Invasion
  • LOXL4
  • MMP2
  • TGF-β1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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

In: Biochemical and Biophysical Research Communications, Vol. 373, No. 4, 05.09.2008, p. 521-527.

Research output: Contribution to journalArticle

Kim, DJ, Lee, DC, Yang, SJ, Lee, JJ, Bae, EM, Kim, DM, Min, SH, Kim, SJ, Kang, DC, Sang, BC, Myung, PK, Park, KC & Yeom, YI 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, vol. 373, no. 4, pp. 521-527. https://doi.org/10.1016/j.bbrc.2008.06.071
Kim, Dong Joon ; Lee, Dong Chul ; Yang, Suk Jin ; Lee, Jung Ju ; Bae, Eun Mi ; Kim, Dong Min ; Min, Sang Hyun ; Kim, Soo Jung ; Kang, Dong Chul ; Sang, Byung Chan ; Myung, Pyung Keun ; Park, Kyung Chan ; Yeom, Young Il. / 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. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 373, No. 4. pp. 521-527.
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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.",
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AU - Lee, Dong Chul

AU - Yang, Suk Jin

AU - Lee, Jung Ju

AU - Bae, Eun Mi

AU - Kim, Dong Min

AU - Min, Sang Hyun

AU - Kim, Soo Jung

AU - Kang, Dong Chul

AU - Sang, Byung Chan

AU - Myung, Pyung Keun

AU - Park, Kyung Chan

AU - Yeom, Young Il

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AB - 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.

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