In the July 3rd online edition of PNAS, M. Sauane et al. from Columibia University College of Physicians and Surgeons reported the results of their study on the ability of the melanoma-differentiation-associated gene-7/interleukin -24 (mda-7/IL-24) to induce apoptosis in melanomas. The investigators noted that their previous study revealed a bystander effect in which malignant cells transfected with mda-7 inhibited growth and apoptosis in neighboring cells within the tumor. Dissecting the underlying mechanism(s), researchers found in the current study that secretion of the MDA-7/IL-24 protein induces an autocrine feedback loop, which results in stabilization of its own mRNA without activating its promoter. The study also revealed that MDA-7/IL-24 protein induces sustained ER stress reflected in the expression of ER stress markers (BiP/GRP78, GRP94, GADD153, and phospho-elf2å) and an increase in the production of reactive oxygen species. The authors concluded that their experimental data demonstrate that "both intracellular and secreted proteins activate similar signaling pathways to induce apoptosis" and cancer-specific killing.