Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression.
Mol Cancer
; 17(1): 155, 2018 10 25.
Article
em En
| MEDLINE
| ID: mdl-30359265
ABSTRACT
Emerging evidence supports the pivotal roles of cancer-associated cachexia in breast cancer progression. However, the mediators and mechanisms that mediate cancer-induced cachexia remain unclear. Here, we show that breast cancer-derived exosomes alter adipocytes and muscle cells in terms of increased catabolism characterized by the release of metabolites. Likewise, tumour cells cocultivated with mature adipocytes or C2C12 exhibit an aggressive phenotype through inducing epithelial-mesenchymal transition. Mechanistically, we show that cancer cell-secreted miR-155 promotes beige/brown differentiation and remodel metabolism in resident adipocytes by downregulating the PPARγ expression, but does not significantly affect biological conversion in C2C12. In vitro the use of propranolol ameliorates tumour exosomes-associated cachectic wasting through upregulating the PPARγ expression. These results demonstrate that cancer-derived exosomes reprogram systemic energy metabolism and accelerate cancer-associated cachexia to facilitate tumour progression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caquexia
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MicroRNAs
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Exossomos
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Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article