The ability of WWOX to affect the transcriptional activity of not only SMAD3 but also of a key transcriptional cofactor such as RUNX2 suggests that the presence or absence of WWOX could be critical for modulating TGFβ signaling and, more importantly, for the activation or repression of specific transcriptional targets known to be associated with tumor progression. This evidence concerns the gene WWOX and neoplasm.