Taking all our data together, we propose a working model as follows: the activation of DR5 normally favors 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 immunosurveillance), but also restrict the formation of another complex, the metastasis and invasion signaling complex (MISC), eventually resulting in suppression of cancer cell invasion and metastasis. Here, TNFRSF10B is linked to cancer.