Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation

Yu, D.C.W., Waby, J.S., Chirakkal, H., Staton, C.A. and Corfe, B.M. (2010) Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation. Molecular Cancer, 9. Art no.276. ISSN 1476-4598

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Abstract

Background: Neuropilin is a transmembrane receptor for vascular endothelial growth factor (VEGF) and is expressed in normal endothelial cells and upregulated in cancer cells. Neuropilin-1 (NRP-1) has been shown to promote tumour cell migration and survival in colon cancer in response to VEGF binding. The expression profiles of neuropilins, associated co-receptors and known ligands have been mapped in three colorectal cell lines: Caco-2, HCT116 & HT29. We have previously shown that butyrate, a naturally occurring histone deacetylase inhibitor (HDACi) produced by fermentation of fibre in the colon, causes apoptosis of colon cancer cell lines.

Results: Here we demonstrate that butyrate down-regulates NRP-1 and VEGF at the mRNA and protein level in colorectal cancer cell lines. NRP-1 is a known transcriptional target of Sp1, whose activity is regulated by acetylation. NRP-1 down-regulation by butyrate was associated with decreased binding affinity of Sp1 for canonical Sp-binding sites in the NRP-1 promoter. siRNA-mediated knock-down of Sp1 implied that Sp1 may have strong DNA binding activity but weak transactivation potential.

Conclusion: The downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre.

Item Type:	Article
Copyright, Publisher and Additional Information:	© 2010 Yu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords:	Endothelial Growth-Factor; Pancreatic-Cancer Cells; Human Colon-Cancer; Repress Transcription; Sodium-Butytrate; Dietary Fiber; Up-Regulation; Angiogenesis; Apoptosis; Activation
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology (Sheffield)
Depositing User:	Miss Anthea Tucker
Date Deposited:	08 Dec 2010 10:36
Last Modified:	08 Feb 2013 17:29
Published Version:	http://dx.doi.org/10.1186/1476-4598-9-276
Status:	Published
Publisher:	BioMed Central
Refereed:	Yes
Identification Number:	10.1186/1476-4598-9-276
URI:	http://eprints.whiterose.ac.uk/id/eprint/42713

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