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Digestive Diseases and Sciences
Published in:

Open Access 21-01-2023 | Hepatocellular Carcinoma | Original Article

TEA Domain Transcription Factor 1 Inhibits Ferroptosis and Sorafenib Sensitivity of Hepatocellular Carcinoma Cells

Authors: Hongmin Li, Haitao Lan, Ming Zhang, Fen Zhao, Ning An, Cheng Yi

Published in: Digestive Diseases and Sciences | Issue 7/2023

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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.
Appendix
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Metadata
Title
TEA Domain Transcription Factor 1 Inhibits Ferroptosis and Sorafenib Sensitivity of Hepatocellular Carcinoma Cells
Authors
Hongmin Li
Haitao Lan
Ming Zhang
Fen Zhao
Ning An
Cheng Yi
Publication date
21-01-2023
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2023
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-023-07824-5

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