Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis.
Cong ChenBojian XieZhaoqing LiLini ChenYongxia ChenJichun ZhouSiwei JuYulu ZhouXun ZhangWenying ZhuoJingjing YangMisha MaoLing XuLinbo WangPublished in: Cell death & disease (2022)
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.
Keyphrases
- cell death
- cell cycle arrest
- drug resistant
- high glucose
- diabetic rats
- genome wide
- multidrug resistant
- drug induced
- induced apoptosis
- climate change
- emergency department
- oxidative stress
- dna methylation
- small molecule
- cell proliferation
- endothelial cells
- acinetobacter baumannii
- papillary thyroid
- gene expression
- combination therapy
- single cell
- signaling pathway
- endoplasmic reticulum stress
- reactive oxygen species
- fatty acid
- smoking cessation
- amino acid
- fluorescent probe