One prominent way that WWOX exerts its tumor suppressor activity is through inhibition of the TGFβ pathway.42,43 Another study has shown that protein–protein interaction between WWOX, through its WW1 domain, and the PPGY motif of SMAD3, leads to the inhibition of SMAD3 transcriptional activity.44 Moreover, the TGFβ pathway was among the significant altered pathways upon introducing WWOX expression in MDA-MB435S cells (Supplementary Table 2). This evidence concerns the gene SMAD3 and neoplasm.