Dysregulated Wnt signaling confers resistance to cuproptosis in cancer cells

Cuproptosis is characterized by the aggregation of lipoylated components of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. Dysregulation of copper homeostasis and resulting cuproptosis induction is an emerging area of interest for cancer therapy. However, mechanisms of cancer cell evasion of cuproptosis are not well understood. Here, we found a link between copper homeostasis regulated by the Wnt pathway and cuproptosis sensitivity, and may provide a precision medicine strategy for cancer treatment by selectively inducing cuproptosis.

铜死亡（Cuproptosis）是一种独特的铜依赖型调控性细胞死亡形式，其特征为三羧酸循环的脂酰化组分发生聚集，随后伴随铁硫簇蛋白的丢失。铜稳态失调及由此引发的铜死亡诱导，是当前癌症治疗领域备受关注的新兴研究方向。然而，癌细胞规避铜死亡的具体机制仍未得到充分阐明。本研究发现了Wnt通路（Wnt pathway）调控的铜稳态与铜死亡敏感性之间的关联，并有望通过选择性诱导铜死亡，为癌症治疗提供精准医学策略。