SMAD4 and cancer: These pathways include various branches of MAPK, Rho-like GTPase signalling and PI3K/AKT pathways.57 ERK, JNK and Rho A regulate TGF-β-induced migration in MCF-7 cells, as well as in the SMAD4-deficient breast cancer cell line MDA-MB-468.58 The cooperation between SMAD and non-SMAD signalling pathways determines the outcome of the cellular response to TGF-β.59 Cancer therapies targeting metabolic pathways have been investigated for many years.