MC3R and cancer: TP53 was transcriptionally activated upon MC3 treatment in HCT116 WT cells, which at least partially accounts for the activation of its target genes, including p21. In p53-null or -mutant cells, however, p21 can be stimulated through pathways other than p53, such as p73, HRAS-Raf-MAPK signaling, the breast cancer susceptibility gene BRCA1, and the TGFβ/SMAD pathway (26).