The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling

In Huntington disease (HD), polyglutamine expansion in the huntingtin protein causes specific neuronal death. The consequences of the presence of mutant huntingtin in other tissues are less well understood. Here we propose that mutant huntingtin influences breast cancer progression. Indeed, we show...

Full description

Bibliographic Details
Main Authors:	Moreira Sousa, Cristovão, McGuire, John Russel, Thion, Morgane Sonia, Gentien, David, de la Grange, Pierre, Tezenas du Montcel, Sophie, Vincent-Salomon, Anne, Durr, Alexandra, Humbert, Sandrine
Format:	Online
Language:	English
Published:	WILEY-VCH Verlag 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569645/

id	pubmed-3569645
recordtype	oai_dc
spelling	pubmed-35696452013-02-12 The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling Moreira Sousa, Cristovão McGuire, John Russel Thion, Morgane Sonia Gentien, David de la Grange, Pierre Tezenas du Montcel, Sophie Vincent-Salomon, Anne Durr, Alexandra Humbert, Sandrine Research Articles In Huntington disease (HD), polyglutamine expansion in the huntingtin protein causes specific neuronal death. The consequences of the presence of mutant huntingtin in other tissues are less well understood. Here we propose that mutant huntingtin influences breast cancer progression. Indeed, we show that mammary tumours appear earlier in mouse breast cancer models expressing mutant huntingtin as compared to control mice expressing wild-type huntingtin. Tumours bearing mutant huntingtin have a modified gene expression pattern that reflects enhanced aggressiveness with the overexpression of genes favouring invasion and metastasis. In agreement, mutant huntingtin accelerates epithelial to mesenchymal transition and enhances cell motility and invasion. Also, lung metastasis is higher in HD conditions than in control mice. Finally, we report that in HD, the dynamin dependent endocytosis of the ErbB2/HER2 receptor tyrosine kinase is reduced. This leads to its accumulation and to subsequent increases in cell motility and proliferation. Our study may thus have important implications for both cancer and HD. WILEY-VCH Verlag 2013-02 2013-01-09 /pmc/articles/PMC3569645/ /pubmed/23300147 http://dx.doi.org/10.1002/emmm.201201546 Text en Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Moreira Sousa, Cristovão McGuire, John Russel Thion, Morgane Sonia Gentien, David de la Grange, Pierre Tezenas du Montcel, Sophie Vincent-Salomon, Anne Durr, Alexandra Humbert, Sandrine
spellingShingle	Moreira Sousa, Cristovão McGuire, John Russel Thion, Morgane Sonia Gentien, David de la Grange, Pierre Tezenas du Montcel, Sophie Vincent-Salomon, Anne Durr, Alexandra Humbert, Sandrine The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling
author_facet	Moreira Sousa, Cristovão McGuire, John Russel Thion, Morgane Sonia Gentien, David de la Grange, Pierre Tezenas du Montcel, Sophie Vincent-Salomon, Anne Durr, Alexandra Humbert, Sandrine
author_sort	Moreira Sousa, Cristovão
title	The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling
title_short	The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling
title_full	The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling
title_fullStr	The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling
title_full_unstemmed	The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling
title_sort	huntington disease protein accelerates breast tumour development and metastasis through erbb2/her2 signalling
description	In Huntington disease (HD), polyglutamine expansion in the huntingtin protein causes specific neuronal death. The consequences of the presence of mutant huntingtin in other tissues are less well understood. Here we propose that mutant huntingtin influences breast cancer progression. Indeed, we show that mammary tumours appear earlier in mouse breast cancer models expressing mutant huntingtin as compared to control mice expressing wild-type huntingtin. Tumours bearing mutant huntingtin have a modified gene expression pattern that reflects enhanced aggressiveness with the overexpression of genes favouring invasion and metastasis. In agreement, mutant huntingtin accelerates epithelial to mesenchymal transition and enhances cell motility and invasion. Also, lung metastasis is higher in HD conditions than in control mice. Finally, we report that in HD, the dynamin dependent endocytosis of the ErbB2/HER2 receptor tyrosine kinase is reduced. This leads to its accumulation and to subsequent increases in cell motility and proliferation. Our study may thus have important implications for both cancer and HD.
publisher	WILEY-VCH Verlag
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569645/
_version_	1611954009955893248

The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling

Similar Items