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CCN5, a novel transcriptional repressor of the transforming growth factor beta signaling pathway

Michèle Sabbah, Céline Prunier, Nathalie Ferrand, Virginie Megalophonos, Kathleen Lambein UGent, Olivier De Wever UGent, Nicolas Nazaret, Joël Lachuer, Sylvie Dumont and Gérard Redeuilh (2011) MOLECULAR AND CELLULAR BIOLOGY. 31(7). p.1459-1469
abstract
CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that the CCN5 protein is localized mostly in the cytoplasm and in part in the nucleus of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor presumably through association with histone deacetylase 1 (HDAC1). Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the transforming growth factor beta (TGF-beta) signaling pathway, prominent among them TGF-beta RII receptor. We show that CCN5 is recruited to the TGF-beta RII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-beta RII gene. Consistent with this finding, CCN5, we found, functions to suppress TGF-beta-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-beta signaling cascade that is known to promote EMT.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
EPITHELIAL-MESENCHYMAL-TRANSITION, HUMAN BREAST-CANCER, ESTROGEN-RECEPTOR-ALPHA, HUMAN PANCREATIC-CANCER, HISTONE DEACETYLASES, CELL-PROLIFERATION, TUMOR-CELLS, E-CADHERIN, GENE, EXPRESSION
journal title
MOLECULAR AND CELLULAR BIOLOGY
Mol. Cell. Biol.
volume
31
issue
7
pages
1459 - 1469
Web of Science type
Article
Web of Science id
000288437100011
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
5.527 (2011)
JCR rank
46/286 (2011)
JCR quartile
1 (2011)
ISSN
0270-7306
DOI
10.1128/MCB.01316-10
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
1843250
handle
http://hdl.handle.net/1854/LU-1843250
date created
2011-06-28 12:29:08
date last changed
2011-07-05 09:01:32
@article{1843250,
  abstract     = {CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that the CCN5 protein is localized mostly in the cytoplasm and in part in the nucleus of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor presumably through association with histone deacetylase 1 (HDAC1). Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the transforming growth factor beta (TGF-beta) signaling pathway, prominent among them TGF-beta RII receptor. We show that CCN5 is recruited to the TGF-beta RII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-beta RII gene. Consistent with this finding, CCN5, we found, functions to suppress TGF-beta-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-beta signaling cascade that is known to promote EMT.},
  author       = {Sabbah, Mich{\`e}le and Prunier, C{\'e}line and Ferrand, Nathalie and Megalophonos, Virginie and Lambein, Kathleen and De Wever, Olivier and Nazaret, Nicolas and Lachuer, Jo{\"e}l and Dumont, Sylvie and Redeuilh, G{\'e}rard},
  issn         = {0270-7306},
  journal      = {MOLECULAR AND CELLULAR BIOLOGY},
  keyword      = {EPITHELIAL-MESENCHYMAL-TRANSITION,HUMAN BREAST-CANCER,ESTROGEN-RECEPTOR-ALPHA,HUMAN PANCREATIC-CANCER,HISTONE DEACETYLASES,CELL-PROLIFERATION,TUMOR-CELLS,E-CADHERIN,GENE,EXPRESSION},
  language     = {eng},
  number       = {7},
  pages        = {1459--1469},
  title        = {CCN5, a novel transcriptional repressor of the transforming growth factor beta signaling pathway},
  url          = {http://dx.doi.org/10.1128/MCB.01316-10},
  volume       = {31},
  year         = {2011},
}

Chicago
Sabbah, Michèle, Céline Prunier, Nathalie Ferrand, Virginie Megalophonos, Kathleen Lambein, Olivier De Wever, Nicolas Nazaret, Joël Lachuer, Sylvie Dumont, and Gérard Redeuilh. 2011. “CCN5, a Novel Transcriptional Repressor of the Transforming Growth Factor Beta Signaling Pathway.” Molecular and Cellular Biology 31 (7): 1459–1469.
APA
Sabbah, Michèle, Prunier, C., Ferrand, N., Megalophonos, V., Lambein, K., De Wever, O., Nazaret, N., et al. (2011). CCN5, a novel transcriptional repressor of the transforming growth factor beta signaling pathway. MOLECULAR AND CELLULAR BIOLOGY, 31(7), 1459–1469.
Vancouver
1.
Sabbah M, Prunier C, Ferrand N, Megalophonos V, Lambein K, De Wever O, et al. CCN5, a novel transcriptional repressor of the transforming growth factor beta signaling pathway. MOLECULAR AND CELLULAR BIOLOGY. 2011;31(7):1459–69.
MLA
Sabbah, Michèle, Céline Prunier, Nathalie Ferrand, et al. “CCN5, a Novel Transcriptional Repressor of the Transforming Growth Factor Beta Signaling Pathway.” MOLECULAR AND CELLULAR BIOLOGY 31.7 (2011): 1459–1469. Print.