2. Academic Validation
  3. Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis

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

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-125506
    99.76%, Fascin Inhibitor