TWIST1 and cancer: The opposing roles of Akt1 and Akt2 during metastatic progression [93, 94] may provide a ration interpretation by proposing a model whereby when cancer cells need to disseminate, Akt2-mediated phosphorylation on S42 of Twist is dominant; whilst during metastatic colonization, Akt1-mediated phosphorylation on T121 and S123 triggers ubiquitination-dependent degradation of Twist and promotes proliferation.