Related Experiment Video
Updated: Jun 4, 2026
06:01
A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Subtype-Specific Alterations in Copper Trafficking Associated with KRAS Mutations in Isogenic Colorectal Cancer Cell
Elina Üveges1,2, Anikó Gaál3, Gergely Szakács4,5
1Integrative Health and Environmental Analysis Research Laboratory, Institute of Chemistry, ELTE Eötvös Loránd University, Budapest, Hungary.
Biological Trace Element Research
|June 2, 2026
Summary
Copper homeostasis varies in KRAS-mutant colorectal cancer cells depending on the specific mutation. Targeting copper metabolism shows promise for treating these cancers, particularly the G12V subtype.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- KRAS-mutant colorectal cancer (CRC) has limited treatment options.
- Copper bioavailability is a potential therapeutic target in KRAS-mutant CRC.
- Understanding copper homeostasis is crucial for developing novel CRC treatments.
Purpose of the Study:
- To investigate copper homeostasis in isogeneic colorectal cancer cell models with distinct KRAS codon 12 mutations (G12C, G12D, G12V).
- To determine the mutation-specific effects of KRAS on copper metabolism in colorectal cancer cells.
- To evaluate the sensitivity of KRAS-mutant CRC cells to copper perturbations.
Main Methods:
- Utilized isogeneic colorectal cancer cell lines with specific KRAS G12C, G12D, and G12V mutations.
- Assessed copper levels, copper uptake, and sensitivity to copper toxicity.
- Measured cellular response to copper chelators and analyzed ATP7A expression.
Main Results:
- Copper homeostasis differs significantly among KRAS-mutant cells in a mutation-specific manner (G12V > G12C > G12D).
- G12V-mutant cells exhibited reduced copper levels, increased uptake, and resistance to copper toxicity.
- Ammonium tetrathiomolybdate inhibited cell growth across all tested KRAS-mutant cell lines.
Conclusions:
- KRAS-mutant colorectal cancer cells display distinct alterations in copper homeostasis based on the specific KRAS mutation.
- Copper metabolism is a promising target for KRAS-mutant colorectal cancer therapy.
- The sensitivity to copper perturbation is mutation-subtype specific, suggesting tailored therapeutic strategies.
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