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(Slides)

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In this study, the researchers investigated the use of a drug called elesclomol to treat lung adenocarcinoma (LUAD) with a specific type of mutation in the KRAS gene (KRASG12). They found that elesclomol can induce a type of cell death called cuproptosis in LUAD cells. Cuproptosis is a form of regulated cell death that is triggered by an excess of copper in the cells.<br /><br />The researchers also discovered that LUAD cells with the KRASG12 mutation are particularly sensitive to elesclomol-copper treatment. They found that the expression of a protein called ATP7A, which is involved in copper metabolism, is associated with the KRASG12 mutation status in LUAD cells. Elesclomol can up-regulate the expression of a protein called RNF207, which interacts with ATP7A. This interaction may be a potential mechanism for regulating the expression of ATP7A.<br /><br />The researchers performed various experiments to investigate the effects of ATP7A, KRAS, and RNF207 on cuproptosis in LUAD cells. They collected tissue samples from LUAD patients and analyzed the expression of ATP7A. They also performed gain- and loss-of-function experiments to study the role of ATP7A, KRAS, and RNF207 in cuproptosis.<br /><br />Overall, the findings of this study suggest that elesclomol transports copper ions into LUAD cells, leading to the activation of endoplasmic reticulum stress and the up-regulation of RNF207. This, in turn, leads to the degradation of ATP7A and increases the retention of copper ions in the cells, ultimately resulting in cuproptosis of KRASG12 mutant LUAD cells.<br /><br />These findings provide insights into the molecular mechanism underlying the therapeutic potential of elesclomol-copper treatment for KRASG12 mutant LUAD. Further research in this area may help in the development of new chemotherapeutic strategies for this subtype of lung cancer.

Asset Subtitle

Zeyi Liu

Meta Tag

Speaker Zeyi Liu

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

elesclomol

lung adenocarcinoma

LUAD

KRAS gene

KRASG12 mutation

cuproptosis

regulated cell death

copper metabolism

ATP7A

RNF207