Cancer-associated Fibroblasts Promote Irradiated Cancer Cell Recovery Through Autophagy.
EBioMedicine
; 17: 45-56, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-28258923
ABSTRACT
Tumor relapse after radiotherapy is a significant challenge to oncologists, even after recent the advances in technologies. Here, we showed that cancer-associated fibroblasts (CAFs), a major component of cancer stromal cells, promoted irradiated cancer cell recovery and tumor relapse after radiotherapy. We provided evidence that CAFs-produced IGF1/2, CXCL12 and ß-hydroxybutyrate were capable of inducing autophagy in cancer cells post-radiation and promoting cancer cell recovery from radiation-induced damage in vitro and in vivo in mice. These CAF-derived molecules increased the level of reactive oxygen species (ROS) post-radiation, which enhanced PP2A activity, repressing mTOR activation and increasing autophagy in cancer cells. Consistently, the IGF2 neutralizing antibody and the autophagy inhibitor 3-MA reduce the CAF-promoted tumor relapse in mice after radiotherapy. Taken together, our findings demonstrated that CAFs promoted irradiated cancer cell recovery and tumor regrowth post-radiation, suggesting that targeting the autophagy pathway in tumor cells may be a promising therapeutic strategy for radiotherapy sensitization.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Fibroblastos
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Neoplasias Hepáticas
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Neoplasias Pulmonares
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Aged80
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Animals
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Humans
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Middle aged
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China