SMAD4 and colorectal carcinoma: It is also noteworthy that atorvastatin treatment of BRAF-mutant mice reduces crypt cell numbers to levels comparable to WT animals, suggesting that statins likely revert the increased proliferation caused by the expression of mutant BRAF. The sensitivity of BRAF-mutant CRC cell lines to statin treatment has also been suggested to depend on BMP signaling through a functional SMAD4 gene61.