2023 World Conference on Lung Cancer (Posters)-P1.02. Targeting ATP7A by Elesclomol-Copper Derived Endoplasmic Reticulum Stress to Mediate Cuproptosis in KRAS-G12 Mutant LUAD

P1.02. Targeting ATP7A by Elesclomol-Copper Derived Endoplasmic Reticulum Stress to Mediate Cuproptosis in KRAS-G12 Mutant LUAD - PDF(Abstract)

Back to course

Pdf Summary

A study presented at the World Conference on Lung Cancer in 2023 explored the role of targeting ATP7A by elesclomol-copper derived endoplasmic reticulum stress in mediating cuproptosis in KRAS-G12 mutant lung adenocarcinoma (LUAD). The researchers investigated the potential of copper metabolism as a therapeutic target for KRAS-driven cancers, as previous studies have shown that excess copper can induce cuproptosis, a form of regulated cell death. The study found that the copper transporter ATP7A was highly expressed in KRAS-G12 mutant LUAD patients and cell lines. They also discovered that elesclomol, a copper ionophore, could induce cuproptosis and down-regulate ATP7A. RNA sequencing revealed that the elesclomol-copper complex could activate endoplasmic reticulum stress and up-regulate the E3 ligase RNF207, which interacts with ATP7A. The researchers performed various experiments, including immunohistochemistry, qRT-PCR, Western blotting, and gain- and loss-of-function studies, to investigate the effects of ATP7A, KRAS, and RNF207 on LUAD cuproptosis. They found that elesclomol mediates cuproptosis in LUAD cells, particularly in KRAS-G12 mutant cells, through the upregulation of RNF207. RNF207 induces the ubiquitination and degradation of ATP7A, leading to increased retention of copper ions in the cells and ultimately mediating cell death. The researchers concluded that targeting copper metabolism could be a promising strategy for the treatment of KRAS-G12 mutant LUAD.

Asset Subtitle

Zeyi Liu

Meta Tag

Speaker Zeyi Liu

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

ATP7A

elesclomol-copper

endoplasmic reticulum stress

cuproptosis

KRAS-G12 mutant

lung adenocarcinoma

copper metabolism

therapeutic target

RNF207

cell death