MAPK4 and neoplasm: Lastly, co-expression of MAPK4D254A and AKT1-DD only partially recapitulated the tumor-promoting activity of WT MAPK4 in the soft-agar assays, suggesting that MAPK4 activation of additional signaling cascade beyond PDK1 and AKT may be important to promote tumor cell anchorage-independent growth (Fig 5G).