Our findings, that apoptosis induced by TRAIL in a small panel of carcinoma cell lines is preferentially induced by TRAIL-R1 together with the demonstration that TRAIL-induced migration is solely triggered by TRAIL-R2 or that TRAIL-R1 is able to contribute to apoptosis induced by ER stress inducers, uncover TRAIL-R1 as an important target for cancer therapy. Here, TNFRSF10B is linked to cancer.