Non-genomic activation of the AKT-mTOR pathway by the mitochondrial stress response in thyroid cancer.
Oncogene
; 41(44): 4893-4904, 2022 Oct.
Article
em En
| MEDLINE
| ID: mdl-36195659
ABSTRACT
Cancer progression is associated with metabolic reprogramming and causes significant intracellular stress; however, the mechanisms that link cellular stress and growth signalling are not fully understood. Here, we identified a mechanism that couples the mitochondrial stress response (MSR) with tumour progression. We demonstrated that the MSR is activated in a significant proportion of human thyroid cancers via the upregulation of heat shock protein D family members and the mitokine, growth differentiation factor 15. Our study also revealed that MSR triggered AKT/S6K signalling by activating mTORC2 via activating transcription factor 4/sestrin 2 activation whilst promoting leucine transporter and nutrient-induced mTORC1 activation. Importantly, we found that an increase in mtDNA played an essential role in MSR-induced mTOR activation and that crosstalk between MYC and MSR potentiated mTOR activation. Together, these findings suggest that the MSR could be a predictive marker for aggressive human thyroid cancer as well as a useful therapeutic target.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Glândula Tireoide
/
Proteínas Proto-Oncogênicas c-akt
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article