Cancer-selective apoptotic effects of extracellular and intracellular Par-4

Selectivity toward cancer cells is the most desirable element in cancer therapeutics. Par-4 is a cancer cell-selective proapoptotic protein that functions intracellularly in the cytoplasmic and nuclear compartments as a tumor suppressor. Moreover, recent findings indicate that the Par-4 protein is secreted by cells, and extracellular Par-4 induces cancer cell-specific apoptosis by interaction with the cell-surface receptor GRP78. This review describes the mechanisms underlying the apoptotic effects of both extracellular and intracellular Par-4 acting through its effector domain SAC.