(i) the levels of energy-metabolism associated transcription factors (ERα and β, HIF-1α, c-MYC, p53, PPAR-γ and PGC1- α); (ii) the protein levels and fluxes of glycolysis and oxidative phosphorylation (OxPhos); and (iii) metastatic ATP-dependent processes such as cell invasiveness and migration were determined by using the multicellular tumor spheroids (MCTS) model, a tridimensional cancer cell model (14). This evidence concerns the gene ESR1 and cancer.