Lactate promoted epithelial–mesenchymal transition (EMT) phenotype through SIRT1-dependent SMAD4 axis in RCC cell lines. Characterization of EMT phenotype after 20 mM lactate, tumor cell-derived CM, and 200µM NAM treatment by Western blot (A). N-cadherin expression with 20 Mm lactate and 200µM NAM by immunofluorescence (B). Co-immunoprecipitation of acetylated lysine/SMAD4 (C) and SMAD4/SNAIL (D) in lactate and nicotinamide treatment conditions. Western blot and immunofluorescence quantification are represented as fold change of 20 mM lactate or 200µM nicotinamide versus control condition Abbreviations: C/CTR—control, CM—conditioned medium, L/LAC—20 mM lactate, N/NAM—200µM nicotinamide, NCAD—N-cadherin, VIM—vimentin.