Based on our findings [42,96], we suggest that the activation of DR5 normally favors the formation of the DISC, resulting in induction of apoptosis or anoikis as well as other potential biological consequences; this will not only lead to direct killing of detached cancer cells (e.g., via anoikis or TRAIL/DR5-mediated immune surveillance) but also restrict the formation of another complex named the metastasis and invasion signaling complex (MISC), eventually resulting in the suppression of cancer cell invasion and metastasis. Here, TNFRSF10B is linked to cancer.