DR5 suppression induces sphingosine-1-phosphate-dependent TRAF2 polyubiquitination leading to activation of JNK/AP-1 and promotion of cancer cell invasion

摘要

BackgroundDeath receptor (DR5), a well-characterized death domain-containing cell surface pro-apoptotic protein, has been suggested to suppress cancer cell invasion and metastasis. However, the underlying mechanisms have not been fully elucidated. Our recent work demonstrates that DR5 suppression promotes cancer cell invasion and metastasis through caspase-8/TRAF2-mediated activation of ERK and JNK signaling and MMP1 elevation. The current study aimed at addressing the mechanism through which TRAF2 is activated in a caspase-8 dependent manner.