Skip to Main content Skip to Navigation
Journal articles

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 hunting-tin 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.
Complete list of metadatas

Cited literature [62 references]  Display  Hide  Download

https://hal.sorbonne-universite.fr/hal-01549113
Contributor : Gestionnaire Hal-Upmc <>
Submitted on : Wednesday, June 28, 2017 - 3:17:13 PM
Last modification on : Friday, December 11, 2020 - 9:36:02 AM
Long-term archiving on: : Wednesday, January 17, 2018 - 8:27:48 PM

File

309.full.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Cristovao Moreira Sousa, John Russel Mcguire, Morgane Sonia Thion, David Gentien, Pierre de la Grange, et al.. The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling. EMBO Molecular Medicine, Wiley Open Access, 2013, 5 (2), pp.309-325. ⟨10.1002/emmm.201201546⟩. ⟨hal-01549113⟩

Share

Metrics

Record views

1083

Files downloads

1112