SMAD3 and cancer: We further found that CPCs derived from Ahr-deficient tumours exhibited very high levels of P-SMAD3 compared to tumours with intact Ahr. Ahr deletion in GCPs together with the cancer-initiating Ptch1 gene deletions dramatically reduced survival, identifying a potent tumour-suppressive role for Ahr. CPCs from these Ahr-deficient tumours were refractory to differentiation in vitro.