Recently, it was observed that Par-4 protein is also spontaneously secreted by normal and cancer cells to the extracellular compartment (cell culture-conditioned medium or circulating in serum) and is able to induce cancer cell-specific apoptosis by interacting with the cell-surface receptor GRP78 and activating the FADD/caspase-8/caspase-3 pathway (19). This evidence concerns the gene CASP8 and cancer.