Fig. 6.

A working model for DR5-mediated suppression of cancer cell invasion. The primary function of DR5 is to mediate apoptosis upon activation through formation of the DISC; this will restrict the formation of another complex, the metastasis and invasion signaling complex (MISC), and subsequently suppress cell invasion. When DR5 is inhibited, available FADD and caspase-8 may recruit and stabilize TRAF2 with the help of S1P, resulting in enhanced TRAF2 polyubiquitination and activation, likely through a self-ubiquitination mechanism. This will further lead to the activation of ERK and JNK signaling and subsequent AP-1-dependent expression and activation of MMPs (e.g., MMP1) and finally, promotion of invasion and metastasis of cancer cells