This study indicates that reduced canonical signalling via the SMADs correlates with high risk phenotypic changes, however, as the TGF-β pathway can also activate non-SMAD pathways such as the Mitogen Activated Protein (MAP) kinase pathway, Rho-like GTPase pathways (RhoA) and Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (AKT) pathways [47], it is possible that, as TGF-β's SMAD-dependent tumour suppressor arm is impaired, pro-tumourigenic non-SMAD pathways dominate to drive invasion and metastasis [48]. Here, AKT1 is linked to neoplasm.