FDX1通过诱导铜死亡抑制甲状腺癌的恶性进展。

FDX1 inhibits thyroid cancer malignant progression by inducing cuprotosis.

作者信息

Chen Gaoxiang, Zhang Jianan, Teng Weifeng, Luo Yong, Ji Xiaochun

机构信息

Department of Thyroid and Breast Surgery, Ningbo Medical Center Lihuili Hospital, No.57 XingNing Road, Ningbo, Zhejiang Province, China.

出版信息

Heliyon. 2023 Jul 26;9(8):e18655. doi: 10.1016/j.heliyon.2023.e18655. eCollection 2023 Aug.

DOI:10.1016/j.heliyon.2023.e18655

PMID:37554785

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10404994/

Abstract

Cuprotosis is a recently identified cell death form that caused by intracellular copper accumulation and regulated by FDX1. This work aimed to explore the role of cuprotosis and the pivotal regulatory gene FDX1 in thyroid cancer development. We observed that expression of FDX1 in tumor section was notably lower than that in non-tumor sections in clinical samples. Induction of cuprotosis by elesclomol (ES) significantly repressed the in vitro and in vivo growth of thyroid cancer cells, simultaneously elevated Cu level and expression of FDX1, whereas depletion of FDX1 abolished these effects. Knockdown of FDX1 decreased the lipoylation level of DLAT and DLST in thyroid cancer cells, alleviated cuprotosis-induced cell death, simultaneously upregulated the levels of PA and α-KG. These findings demonstrated that FDX1 promotes the cuprotosis of thyroid cancer cells via regulating the lipoylation of DLAT.

摘要

铜死亡是一种最近被发现的细胞死亡形式，由细胞内铜积累引起并受FDX1调节。这项工作旨在探讨铜死亡及其关键调节基因FDX1在甲状腺癌发展中的作用。我们观察到，临床样本中肿瘤切片中FDX1的表达明显低于非肿瘤切片。用依斯氯铵（ES）诱导铜死亡显著抑制了甲状腺癌细胞的体外和体内生长，同时提高了铜水平和FDX1的表达，而敲低FDX1则消除了这些作用。敲低FDX1降低了甲状腺癌细胞中DLAT和DLST的硫辛酰化水平，减轻了铜死亡诱导的细胞死亡，同时上调了PA和α-KG的水平。这些发现表明，FDX1通过调节DLAT的硫辛酰化促进甲状腺癌细胞的铜死亡。