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MCF-7 Drug Resistant Cell Lines Switch Their Lipid Metabolism to Triple Negative Breast Cancer Signature.

ABSTRACT: Obesity and adipose tissue have been closely related to a poor cancer prognosis, especially in prostate and breast cancer patients. The ability of transferring lipids from the adipose tissue to the tumor cells is actively linked to tumor progression. However, different types of breast tumor seem to use these lipids in different ways and metabolize them in different pathways. In this study we have tracked by mass spectrometry how palmitic acid from the adipocytes is released to media being later incorporated in different breast cancer cell lines (MDA-MB-231, SKBR3, BT474, MCF-7 and its resistant MCF-7 EPI^R and MCF-7 TAX^R). We have observed that different lines metabolize the palmitic acid in a different way and use their carbons in the synthesis of different new lipid families. Furthermore, we have observed that the lipid synthesis pattern varied according to the cell line. Surprisingly, the metabolic pattern of the resistant cells was more related to the TNBC cell line compared to their sensitive cell line MCF-7. These results allow us to determine a specific lipid pattern in different cell lines that later might be used in breast cancer diagnosis and to find a better treatment according to the cancer molecular type.

SUBMITTER: Adria-Cebrian J

PROVIDER: S-EPMC8657222 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:At present, a large number of exciting results have been found regarding energy metabolism within the triple‑negative breast cancer (TNBC) field. Apart from aerobic glycolysis, a number of other catabolic pathways have also been demonstrated to participate in energy generation. However, the prognostic value of energy metabolism for TNBC currently remains unclear. In the present study, the association between gene expression profiles of energy metabolism and outcomes in patients with TNBC was examined using datasets obtained from the Gene Expression Omnibus and The Cancer Genome Atlas. In total, four robust TNBC subtypes were identified on the basis of negative matrix factorization clustering and gene expression patterns, which exhibited distinct immunological, molecular and prognostic (disease‑free survival) features. The differentially expressed genes were subsequently identified from the subgroup that demonstrated the poorest prognosis compared with the remaining 3 subgroups, where their biological functions were assessed further by means of gene ontology enrichment analysis. Any signatures found to be associated with energy metabolism were then established using the Cox proportional hazards model to assess patient prognosis. According to results of Kaplan‑Meier analysis, the constructed signature consisting of eight genes that were associated with energy metabolism distinguished patient outcomes into low‑ and high‑risk groups. In addition, this signature, which was found to be markedly associated with the clinical characteristics of the patients, served as an independent factor in predicting TNBC patient prognosis. According to gene set enrichment analysis, the gene sets related to the high‑risk group participated in the MAPK signal transduction pathway, focal adhesion and extracellular matrix receptor interaction, whilst those related to the low‑risk group were revealed to be mainly associated with mismatch repair and propanoate metabolism. Findings from the present study shed new light on the role of energy metabolism within TNBC, where the eight‑gene signature associated with energy metabolism constructed can be utilized as a new prognostic marker for predicting survival in patients with TNBC.

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MCF-7 Drug Resistant Cell Lines Switch Their Lipid Metabolism to Triple Negative Breast Cancer Signature.

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