Year: 2024
Type: dissertation
Abstract: Altered metabolism is a hallmark of cancer. Amino acid metabolism is often disrupted in tumours to meet increased demands for building blocks and energy. This dissertation explores the role of amino acids in breast cancer cell metabolism using various -omics techniques and bioinformatics to identify potential chemotherapeutic targets. Objectives included examining the role of branched-chain amino acids (BCAAs) in cellular energetics and mevalonate biosynthesis using isotopically labelled amino acids in breast cancer cells, comparing BCAA metabolism in the blood plasma of breast cancer patients and healthy controls, and identifying alterations in amino acid metabolism by integrating metabolomic and transcriptomic data. Methods used were UPLC-ESI-MS/MS, isotope labelling, RNA sequencing, wound healing assay, and integrated genome-metabolome analysis. Results show that 34 % and 14 % of energy in MCF-7 and BCC breast cancer cells, respectively, come from BCAA degradation. Additionally, 67 % and 22 % of carbon in leucine is converted to mevalonate in MCF-7 and BCC cells, respectively. Inhibition of BCAA metabolism reduces breast cancer cell invasiveness. Three BCAA metabolites - 3-hydroxyisovalerate, 3-hydroxyisobutyrate, and mevalonate - are potential biomarkers for early breast cancer detection. Genes AHCY, PHGDH, PSPH, and CHAC1 in methionine and serine metabolism are potential drug targets for breast cancer.
Author: Pankevičiūtė-Bukauskienė, Monika
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7132118162