Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis

  • Cell Death Dis. 2022 Feb 14;13(2):150. doi: 10.1038/s41419-022-04579-1.
Cong Chen   #  1  2 ,  Bojian Xie   #  1  2  3 ,  Zhaoqing Li   #  1  2 ,  Lini Chen  1  2 ,  Yongxia Chen  1  2 ,  Jichun Zhou  1  2 ,  Siwei Ju  1  2 ,  Yulu Zhou  1  2 ,  Xun Zhang  1  2 ,  Wenying Zhuo  1  2 ,  Jingjing Yang  1  2 ,  Misha Mao  1  2 ,  Ling Xu  1  2 ,  Linbo Wang  4  5
Affiliations
  • 1. Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2. Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
  • 3. Department of Surgical Oncology, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.
  • 4. Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
  • 5. Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China. [email protected].
  • # Contributed equally.
PMID: 35165254 DOI: 10.1038/s41419-022-04579-1
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.

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