RT info:eu-repo/semantics/article T1 Multi-omics analysis revealed increased de novo synthesis of serine and lower activity of the methionine cycle in breast cancer cell lines A1 Pankevičiūtė Bukauskienė, Monika A1 Mikalayeva, Valeryia A1 Žvikas, Vaidotas A1 Skeberdis, Vytenis Arvydas A1 Bordel Velasco, Sergio K1 Breast - Cancer K1 Mamas - Cáncer K1 Cancer research K1 Pharmacology K1 Toxicology K1 Drugs - Therapeutic use K1 Medicamentos K1 Metabolomics K1 Metabolism - Research K1 Medical genetics K1 Genética médica K1 3209 Farmacología K1 3214 Toxicología K1 32 Ciencias Médicas AB A pipeline for metabolomics, based on UPLC-ESI-MS, was tested on two malignant breast cancer cell lines of the sub-types ER(+), PR(+), and HER2(3+) (MCF-7 and BCC), and one non-malignant epithelial cancer cell line (MCF-10A). This allowed us to quantify 33 internal metabolites, 10 of which showed a concentration profile associated with malignancy. Whole-transcriptome RNA-seq was also carried out for the three mentioned cell lines. An integrated analysis of metabolomics and transcriptomics was carried out using a genome-scale metabolic model. Metabolomics revealed the depletion of several metabolites that have homocysteine as a precursor, which was consistent with the lower activity of the methionine cycle caused by lower expression of the AHCY gene in cancer cell lines. Increased intracellular serine pools in cancer cell lines appeared to result from the over-expression of PHGDH and PSPH, which are involved in intracellular serine biosynthesis. An increased concentration of pyroglutamic acid in malignant cells was linked to the overexpression of the gene CHAC1. PB MDPI SN 1420-3049 YR 2023 FD 2023 LK https://uvadoc.uva.es/handle/10324/65786 UL https://uvadoc.uva.es/handle/10324/65786 LA eng NO Molecules, 2023, Vol. 28, Nº. 11, 4535 NO Producción Científica DS UVaDOC RD 25-dic-2024