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

被引：51

作者：

Chen, Cong ^{[1
,2
,3
]}

Xie, Bojian ^{[1
,2
,3
,4
]}

Li, Zhaoqing ^{[1
,2
,3
]}

Chen, Lini ^{[1
,2
,3
]}

Chen, Yongxia ^{[1
,2
,3
]}

Zhou, Jichun ^{[1
,2
,3
]}

Ju, Siwei ^{[1
,2
,3
]}

Zhou, Yulu ^{[1
,2
,3
]}

Zhang, Xun ^{[1
,2
,3
]}

Zhuo, Wenying ^{[1
,2
,3
]}

Yang, Jingjing ^{[1
,2
,3
]}

Mao, Misha ^{[1
,2
,3
]}

Xu, Ling ^{[1
,2
,3
]}

Wang, Linbo ^{[1
,2
,3
]}

机构：

[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Surg Oncol, Hangzhou, Peoples R China

[2] Biomed Res Ctr, Hangzhou, Peoples R China

[3] Key Lab Biotherapy Zhejiang Prov, Hangzhou, Peoples R China

[4] Wenzhou Med Univ, Taizhou Hosp, Dept Surg Oncol, Taizhou, Peoples R China

来源：

CELL DEATH & DISEASE | 2022年 / 13卷 / 02期

基金：

中国国家自然科学基金;

关键词：

EXPRESSION; RESISTANCE; CARCINOMA; CELLS;

D O I：

10.1038/s41419-022-04579-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：14

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