Loss of a cell polarity regulator partitioning defective homolog D (ParD6), inhibition of tumor growth factor beta receptor 1 (TGFBR1), and attenuation of mothers against decapentaplegic homolog 2 (SMAD2) expression accelerates the generation of CRC cell populations capable of apical budding, suggesting that interference with apical–basal polarity drives peritoneal dissemination. The gene discussed is SMAD2; the disease is colorectal carcinoma.