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

EMBO Molecular Medicine

Cristovão Moreira Sousa³  John Russel McGuire³  Morgane Sonia Thion³  David Gentien³  Pierre de la Grange¹  Sophie Tezenas du Montcel²  Anne Vincent-Salomon³  Alexandra Durr⁴ 

[1] GenoSplice Technology, Institut Universitaire d'hématologie, Paris, France;AP-HP, Charles-Foix Clinical Research Unit, Department of Biostatistics and Medical Informatics, Hôpital de la Salpêtrière, University Pierre et Marie Curie, Paris, France;Institut Curie, Paris, France;Département de Génétique et Cytogénétique, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, University Pierre et Marie Curie Pierre, UMR-S975, Paris, France

关键词: breast cancer;    dynamin;    huntingtin;    migration;    polyglutamine;   

DOI  :  10.1002/emmm.201201546

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
Copyright © 2013 EMBO Molecular Medicine

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