SMAD2 and breast cancer: This unique effect of EZH2 in promoting bone metastasis may result from dramatically higher TGFβ expression in bone metastasis than that in metastases of other organs and in primary mammary tumors (Supplementary Fig. 6h), i.e., the enriched TGFβ effectively activate the EZH2/integrin β1/FAK/p-Smad2 axis to upregulate PTHLH in bone metastasis.