USP7-mediated ERß stabilization mitigates ROS accumulation and promotes osimertinib resistance by suppressing PRDX3 SUMOylation in non-small cell lung carcinoma.
Cancer Lett
; 582: 216587, 2024 02 01.
Article
em En
| MEDLINE
| ID: mdl-38097136
ABSTRACT
Osimertinib resistance is regarded as a major obstacle limiting survival beneï¬ts for patients undergoing treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, the underlying mechanisms of acquired resistance remain unclear. In this study, we report that estrogen receptor ß (ERß) is highly expressed in osimertinib-resistant NSCLC and plays a pivotal role in promoting osimertinib resistance. We further identified ubiquitin-specific protease 7 (USP7) as a critical binding partner that deubiquitinates and upregulates ERß in NSCLC. ERß promotes osimertinib resistance by mitigating reactive oxygen species (ROS) accumulation. We found that ERß mechanistically suppresses peroxiredoxin 3 (PRDX3) SUMOylation and thus confers osimertinib resistance onto NSCLC. Furthermore, we provide evidence showing that depletion of ERß induces ROS accumulation and reverses osimertinib resistance in NSCLC both in vitro and in vivo. Thus, our results demonstrate that USP7-mediated ERß stabilization suppresses PRDX3 SUMOylation to mitigate ROS accumulation and promote osimertinib resistance, suggesting that targeting ERß may be an effective therapeutic strategy to overcome osimertinib resistance in NSCLC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Acrilamidas
/
Carcinoma Pulmonar de Células não Pequenas
/
Indóis
/
Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article