EGFR inhibition reverses epithelialmesenchymal transition, and decreases tamoxifen resistance via Snail and Twist downregulation in breast cancer cells.
Oncol Rep
; 47(6)2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35445730
ABSTRACT
Tamoxifen resistance remains a major obstacle in the treatment of estrogen receptor (ER)positive breast cancer. In recent years, the crucial role of the epithelialmesenchymal transition (EMT) process in the development of drug resistance in breast cancer has been underlined. However, the central molecules inducing the EMT process during the development of tamoxifen resistance remain to be elucidated. In the present study, it was demonstrated that tamoxifenresistant breast cancer cells underwent EMT and exhibited an enhanced cell motility and invasive behavior. The inhibition of snail family transcriptional repressor 1 (Snail) and twist family BHLH transcription factor 1 (Twist) reversed the EMT phenotype and decreased the tamoxifen resistance, migration and invasion of tamoxifenresistant breast cancer cells. In addition, it was observed that the inhibition of epidermal growth factor receptor (EGFR) reversed the EMT phenotype in tamoxifenresistant MCF7 (MCF7/TR) cells via the downregulation of Snail and Twist. Notably, the EGFR inhibitor, gefitinib, decreased tamoxifen resistance, migration and invasion through the inhibition of Snail and Twist. On the whole, the results of the present study suggest that EGFR may be a promising therapeutic target for tamoxifenresistant breast cancer. Moreover, it was suggested that gefitinib may serve as a potent novel therapeutic strategy for breast cancer patients, who have developed tamoxifen resistance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
/
Neoplasias da Mama
Limite:
Female
/
Humans
Idioma:
En
Revista:
Oncol Rep
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão