TEA Domain Transcription Factor 1 Inhibits Ferroptosis and Sorafenib Sensitivity of Hepatocellular Carcinoma Cells.
Dig Dis Sci
; 68(7): 3070-3082, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-36680650
ABSTRACT
BACKGROUND:
Ferroptosis, as a unique form of cell death, plays crucial negative roles in tumorigenesis and progression. This study aimed to investigate the role and molecular mechanism of TEA domain transcription factor 1 (TEAD1) in HCC and its effect on sorafenib-induced ferroptosis.METHODS:
TEAD1 expression was analyzed in HCC tissues using quantitative PCR, and western blot. The effects on cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. Intracellular iron, reactive oxygen species (ROS), malondialdehyde (MDA) and GSH measurement was used to assess ferroptosis. Chromatin immunoprecipitation and luciferase reporter gene assays were performed to verify the relationship between TEAD1 and solute carrier family 3 member 2 (SLC3A2). Expression of mTOR, ribosomal protein S6, glutathione peroxidase 4 (GPX4) and SLC3A2 was analyzed by western blot. Tumor xenografts were used assess the effect of TEAD1 on tumor growth in vivo.RESULTS:
TEAD1 was more abundant in HCC compared with normal tissues. Overexpression of TEAD1 enhanced the proliferation, migration, and invasion of HCC cells, while knockdown of TEAD1 inhibited these cell behaviors. Further, TEAD1 inhibited ferroptosis, which was demonstrated by decreased intracellular Fe2+ content, ROS, and MDA levels, and increased GSH activity. Mechnistically, TEAD1 promotes the transcription of SLC3A2 and activates the mTOR signaling. Additionally, silenced TEAD1 restrained tumor growth and enhance sorafenib-induced antitumor activity in vivo.CONCLUSIONS:
TEAD1 confers resistance of HCC cells to ferroptosis, thereby promoting the progression of HCC, suggesting the potential value of TEAD1 in the diagnosis and treatment of HCC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Ferroptose
/
Neoplasias Hepáticas
/
3,4-Metilenodioxianfetamina
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article