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- Title
Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis.
- Authors
Chen, Cong; Xie, Bojian; Li, Zhaoqing; Chen, Lini; Chen, Yongxia; Zhou, Jichun; Ju, Siwei; Zhou, Yulu; Zhang, Xun; Zhuo, Wenying; Yang, Jingjing; Mao, Misha; Xu, Ling; Wang, Linbo
- Abstract
Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. In the present study, we investigated the expression profiles and biological effects of fascin actin-bundling protein 1 (Fascin, gene name FSCN1) in breast cancer. In addition, bioinformatics analysis of the TCGA cancer database and gain- and loss-of-function studies showed that Fascin enhances sensitivity to erastin-induced ferroptosis. Mechanistically, Fascin directly interacts with cysteine/glutamate transporter (xCT, gene name SLC7A11) and decreases its stability via the ubiquitin-mediated proteasome degradation pathway. Furthermore, we observed that Fascin is substantially upregulated in tamoxifen-resistant breast cancer cell lines, and drug-resistant cells were also more vulnerable to erastin-induced ferroptosis. Taken together, our findings reveal a previously unidentified role of Fascin in ferroptosis by regulating xCT. Thus, ferroptosis activation in breast cancer with high Fascin level may serve as a potential treatment.
- Publication
Cell Death & Disease, 2022, Vol 13, Issue 2, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-022-04579-1