Increases in TGF-β2 mRNA and protein could be recapitulated by 12–24 h exposure of native cancer cells to acidic pH 6.5 (Fig. 3d and Supplementary Fig. 3e) and further evidence of the activation of TGF-β2 signaling pathway in acidosis-adapted cancer cells was obtained by documenting an increase in the extent of phospho-Smad2/3 (Fig. 3e and Supplementary Fig. 3f). Here, SMAD2 is linked to cancer.