SMAD4 and colorectal carcinoma: Additionally, as the majority of CRC cells usually have null SMAD4 expressions in microsatellite instability (MSI)-negative CRC cell lines, including HT-29 and SW-480, but not for MSI-positive cell lines such as DLD-1, and this depends on SMAD-independent pathways such as JNK pathway [40,41], the JNK pathway has unique importance in EMT induction of CRC.