Skeletal muscle reprogramming by breast cancer regardless of treatment history or tumor molecular subtype

Increased susceptibility to fatigue is a negative predictor of survival commonly experienced by women with breast cancer (BC). Here, we sought to identify molecular changes induced in human skeletal muscle by BC regardless of treatment history or tumor molecular subtype using RNA-sequencing (RNA-seq...

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Bibliographic Details
Published in:NPJ breast cancer 2020, Vol.6 (1), p.18-18, Article 18
Main Authors: Wilson, Hannah E, Stanton, David A, Montgomery, Cortney, Infante, Aniello M, Taylor, Matthew, Hazard-Jenkins, Hannah, Pugacheva, Elena N, Pistilli, Emidio E
Format: Article
Language:English
Subjects:
Breast cancer
Gene expression
Musculoskeletal system
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Summary:Increased susceptibility to fatigue is a negative predictor of survival commonly experienced by women with breast cancer (BC). Here, we sought to identify molecular changes induced in human skeletal muscle by BC regardless of treatment history or tumor molecular subtype using RNA-sequencing (RNA-seq) and proteomic analyses. Mitochondrial dysfunction was apparent across all molecular subtypes, with the greatest degree of transcriptomic changes occurring in women with HER2/neu-overexpressing tumors, though muscle from patients of all subtypes exhibited similar pathway-level dysregulation. Interestingly, we found no relationship between anticancer treatments and muscle gene expression, suggesting that fatigue is a product of BC per se rather than clinical history. In vitro and in vivo experimentation confirmed the ability of BC cells to alter mitochondrial function and ATP content in muscle. These data suggest that interventions supporting muscle in the presence of BC-induced mitochondrial dysfunction may alleviate fatigue and improve the lives of women with BC.
ISSN:2374-4677
2374-4677
DOI:10.1038/s41523-020-0162-2