Understanding the Role of the Death Receptor 5/FADD/caspase-8 Death Signaling in Cancer Metastasis.

The normal function of the extrinsic apoptotic pathway is to mediate apoptosis. Thus, this pathway is generally recognized to be critical in host immune surveillance against cancer. However, many studies have suggested that some key components in this pathway including Fas, death receptor 5 (DR5), Fas-associated death domain (FADD) and caspase-8 may contribute to cancer growth or metastasis. Our recent study on DR5 and caspase-8 expression in human head and neck cancer tissues indicate that high caspase-8 either alone or along with high DR5 in tumor tissue from patients with lymph node metastasis is significantly associated with poor disease-free survival and overall survival, suggesting that these proteins may be involved in positive regulation of cancer metastasis. Thus, efforts should be made to better understand the role of the death receptor 5/FADD/caspase-8 death signaling in regulation of cancer metastasis.