Multi-Omics Analysis Revealed Increased De Novo Synthesis of Serine and Lower Activity of the Methionine Cycle in Breast Cancer Cell Lines

Autor: Monika Pankevičiūtė-Bukauskienė, Valeryia Mikalayeva, Vaidotas Žvikas, V. Arvydas Skeberdis, Sergio Bordel
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecules, Vol 28, Iss 11, p 4535 (2023)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules28114535
Popis: 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.
Databáze: Directory of Open Access Journals
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