title: The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling.
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.
authors.affiliation: Institut Curie, Paris, France; CNRS UMR 3306, Orsay, France.
authors.forename: Cristovão
authors.initials: C
authors.lastname: Moreira Sousa
authors.forename: John Russel
authors.initials: JR
authors.lastname: McGuire
authors.forename: Morgane Sonia
authors.initials: MS
authors.lastname: Thion
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.forename: Pierre
authors.initials: P
authors.lastname: de la Grange
authors.forename: Sophie
authors.initials: S
authors.lastname: Tezenas du Montcel
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Sandrine
authors.initials: S
authors.lastname: Humbert
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C086055:HTT protein, human