We previously showedthat the hormone-activated nuclear receptor (NR) Retinoid X Receptor(RXR) is important for the maintenance of cell identity in CRC.42 Other NRs, such as the Farnesoid X Receptor(FXR) and the thyroid hormone receptor (TR), are involved in the controlof CSC proliferation and differentiation as well.99,100 Together, this suggests a role for SMAD4 in the maintenance of cellularidentity by controlling NR activity through the regulation of ligandavailability. This evidence concerns the gene SMAD4 and colorectal carcinoma.