Role of Par-4 in prostate cancer

Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein that induces apoptosis selectively in cancer cells. This specificity toward cancer cells is attributed to the effector domain of Par-4 known as "Selective for apoptosis in cancer cells" (SAC) domain. Par-4 sensitizes cells to the action of diverse apoptotic stimuli that ultimately causes tumor regression. Recent studies have shown that the Par-4 protein is spontaneously secreted by normal and cancer cells, and extracellular Par-4 induces apoptosis by interacting with the cell-surface receptor Glucoseregulated protein 78 (GRP78). GRP78 is a resident protein in the endoplasmic reticulum (ER) that selectively translocates to the surface of cancer cells. This article emphasizes the role of Par-4, as well as the SAC in apoptosis and tumor resistance in mice. SAC transgenic mice, which are resistant to spontaneous as well as autochthonous tumors are described, along with mechanistic insights gained from the interaction of Par-4/SAC and GRP78. The cancer-selective traits of Par-4/SAC make it an ideal choice for cancer therapeutics.