SMAD3 and cancer: As dox alone has inhibitory effect on cancer cell (breast, prostate and colorectal) growth,28–30 to avoid the confounding effect of dox on outgrowth, we independently assessed 3D outgrowth of untreated (represents Pfn1-proficient condition) and dox-treated (represents Pfn1-depleted condition) MDA-231 cells without or with SMAD3 KD using with a second siRNA (SMAD3 siRNA #2).