FDX1 inhibits thyroid cancer malignant progression by inducing cuprotosis

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.

Keywords

• Thyroid cancer
• Cuprotosis
• FDX1
• DLAT
• Lipoylation