Considering our previous [11] and current findings, we propose a working model as follows: the activation of DR5 favors formation of the death-inducing signaling complex (DISC), resulting in induction of apoptosis or anoikis as well as other potential biological consequences; this not only leads to the direct killing of detached cancer cells (e.g., via anoikis or TRAIL/DR5-mediated immunosurveillance), but also restricts the formation of the metastasis and invasion signaling complex (MISC), eventually resulting in suppression of cancer cell invasion and metastasis. The gene discussed is TNFRSF10B; the disease is cancer.