Since SMAD4-209 originates from promoter C and SMAD4-213 from promoter D, we investigated the activity pattern of SMAD4 promoters and found their differential activity in CRC: promoter C had higher activity in non-malignant cells while promoter D had higher activity in malignant cells, which was confirmed by our transcriptomics data. Here, SMAD4 is linked to colorectal carcinoma.