Cuproptosis: the mechanisms of copper-induced cell death and its implication in colorectal cancer

Abstract

Colorectal cancer (CRC) represents a prevalent neoplastic disorder of the digestive tract, characterized by elevated incidence and mortality rates. The cellular metabolism of copper within CRC cells is frequently dysregulated, indicating that modifications to copper concentrations may induce cell death and potentially enhance the overall suppression of tumor progression. Cuproptosis, a recently identified form of cellular death, occurs when copper ions bind directly to the lipoylated components of the citric acid cycle (CAC) within mitochondrial respiration, thereby disrupting the balance of iron-sulfur cluster (Fe-S cluster) proteins and ultimately leading to protein toxic stress. The defining traits of cuproptosis include dependence on Cu2⁺ concentrations and pronounced expression in cells engaged in mitochondrial respiration. This novel mechanism has attracted significant interest within the cancer research community due to its substantial therapeutic potential in oncology. Treatments based on copper demonstrate an inhibitory effect on tumor proliferation and may facilitate approaches for treating tumors that are resistant to conventional chemotherapy. This article aims to review the significance of cuproptosis in CRC, positing that it may serve as a promising strategy for antitumor therapy and an innovative treatment paradigm to address drug resistance in cancer.

Keywords: CRC; Cell death; Colorectal cancer; Copper; Cuproptosis.