Although our study indicates that the inhibitory effects of RGS6 on TGF-β-induced EMT events in the in vitro system depends on its interaction with SMAD4 (Fig. 6), this novel tumor-suppressing action of RGS6 may not be the only one underlying its protective role against TGF-β-promoted in vivo NSCLC metastases (Fig. 3). This evidence concerns the gene SMAD4 and neoplasm.