Collectively, the results from SMAD3 perturbation experiments suggest that while SMAD3 upregulation can potentially partly contribute to suppression of outgrowth, additional proliferation-restraining mechanisms are likely operative in conjunction with SMAD3 to account for the outgrowth-deficient phenotype of BCC cells upon depletion of Pfn1. The gene discussed is PFN1; the disease is skin basal cell carcinoma.