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

doi:10.1016/j.bbrc.2008.06.071

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 journal › Article › peer-review

23 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 language	English (US)
Pages (from-to)	521-527
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	373
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.06.071
State	Published - Sep 5 2008
Externally published	Yes

Keywords

Invasion
LOXL4
MMP2
TGF-β1

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.06.071

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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

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

@article{7972a953c8e947e88333dd302bed6776,

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",

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.",

keywords = "Invasion, LOXL4, MMP2, TGF-β1",

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

note = "Funding Information: This work was supported by the Korean Systems Biology Research grant from Korea Ministry of Science and Technology and by a grant from Korea Food and Drug Administration. ",

year = "2008",

month = sep,

day = "5",

doi = "10.1016/j.bbrc.2008.06.071",

language = "English (US)",

volume = "373",

pages = "521--527",

journal = "Biochemical and Biophysical Research Communications",

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TY - JOUR

T1 - 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

AU - Kim, Dong Joon

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

N1 - Funding Information: This work was supported by the Korean Systems Biology Research grant from Korea Ministry of Science and Technology and by a grant from Korea Food and Drug Administration.

PY - 2008/9/5

Y1 - 2008/9/5

N2 - 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.

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.

KW - Invasion

KW - LOXL4

KW - MMP2

KW - TGF-β1

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DO - 10.1016/j.bbrc.2008.06.071

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C2 - 18586005

AN - SCOPUS:50949129818

SN - 0006-291X

VL - 373

SP - 521

EP - 527

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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