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- W4308451279 abstract "Several biological processes related to cancer malignancy are regulated by 17-β estradiol (E2) in ER+-breast cancer. To establish the role of E2 on the atypical cancer energy metabolism, a systematic study analyzing transcription factors, proteins, and fluxes associated with energy metabolism was undertaken in multicellular tumor spheroids (MCTS) from human ER+ MCF-7 breast cancer cells. At E2 physiological concentrations (10 and 100 nM for 24 h), both ERα and ERβ receptors, and their protein target pS2, increased by 0.6-3.5 times vs . non-treated MCTS, revealing an activated E2/ER axis. E2 also increased by 30-470% the content of several transcription factors associated to mitochondrial biogenesis and oxidative phosphorylation (OxPhos) (p53, PGC1-α) and glycolytic pathways (HIF1-α, c-MYC). Several OxPhos and glycolytic proteins (36-257%) as well as pathway fluxes (48-156%) significantly increased being OxPhos the principal ATP cellular supplier (>75%). As result of energy metabolism stimulation by E2, cancer cell migration and invasion processes and related proteins (SNAIL, FN, MM-9) contents augmented by 24-189% vs. non-treated MCTS. Celecoxib at 10 nM blocked OxPhos (60%) as well as MCTS growth, cell migration and invasiveness (>40%); whereas the glycolytic inhibitor iodoacetate (0.5 µM) and doxorubicin (70 nM) were innocuous. Our results show for the first time using a more physiological tridimensional cancer model, resembling the initial stages of solid tumors, that anti-mitochondrial therapy may be useful to deter hormone-dependent breast carcinomas." @default.
- W4308451279 created "2022-11-12" @default.
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- W4308451279 date "2022-11-07" @default.
- W4308451279 modified "2023-10-18" @default.
- W4308451279 title "17-β Estradiol up-regulates energy metabolic pathways, cellular proliferation and tumor invasiveness in ER+ breast cancer spheroids" @default.
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- W4308451279 doi "https://doi.org/10.3389/fonc.2022.1018137" @default.
- W4308451279 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36419896" @default.
- W4308451279 hasPublicationYear "2022" @default.