Specifically, stiffening the ECM neutralises the antagonistic action of SMAD3 on cell proliferation.27 Given our findings that depletion of Pfn1 leads to outgrowth defect of BCC in BME matrix and this can be rescued by stiffening of ECM through addition of collagen-I, we asked whether these phenotypes are correlated with alterations in SMAD3 activation. The gene discussed is SMAD3; the disease is skin basal cell carcinoma.