TWEAK signals through JAK-STAT to induce tumor cell apoptosis

► IFNγ enhancement of TWEAK/Fn14-mediated apoptosis requires JAK-STAT signaling. ► IFNγ treatment results in upregulation of Fn14 expression on tumor cells. ► TWEAK induces pSTAT-1, and TWEAK-induced apoptosis is JAK-STAT dependent. ► TWEAK-mediated STAT signaling occurs via induction of IFNβ. ► An Fn14 agonistic antibody induces pSTAT-1 in xenograft tumors.