Akt/PKB Functions in Cell Migration and Invasion

Cell migration is an enormously complex process that requires sophisticated regulation and exquisite coordination of many cellular proteins that must act in a temporally and spatially orchestrated manner to achieve directional motion. Much like neuromuscular control of gait and walking, except within a single cell, a series of rapid feedback mechanisms must act in a cyclical manner to result in movement. The protein-serine kinase Akt/PKB that acts downstream of phosphatidylinositol 3' kinase (PI3K) activation is intricately involved in normal cell migration and in aberrant movement (e.g., cancer metastasis), but its role can be either pro- or anti-migration depending on cellular context. These contradictory effects likely reflect the nature of cellular motion, in that perturbations that disturb the continuity or integrity of migratory machines tend to be inhibitory. In contrast, increasing overall efficiency/coordination of the processes results in greater mobility. The net result of modulating Akt/PKB is therefore highly dependent upon other inputs into the cell and their context. Here, we briefly describe the molecular events associated with cellular migration, then describe current knowledge of Akt/PKB targets involved in this process, and conclude by discussing implications for suppression of cancer dissemination.