CD95 and CD95L promote and protect cancer stem cells (Nature Communications 2014, Doi: 10.1038/ncomms6238)

報告日期: 2015/03/20
報告時間: 16:00/16:50
報告學生: 蔡鐙墴(以英文報告)
講評老師: 張志鵬
附件下載: 下載[1476-1425858524-1.pdf] 

CD95 and CD95L promote and protect cancer stem cells

Paolo Ceppi, Abbas Hadji, Marcus E. Peter et.

Nat Commun. 2014 Nov 4;5:5238.

Speaker: Teng-Huang Tsai                                             Date: 2015.03.20

Commentator:Chih-Peng Chang, Ph.D.                                  Place: Room 602


CD95 (also called Fas and APO-1) is a prototypical death receptor that regulates tissue homeostasis mainly in the immune system through the induction of apoptosis. Therefore, during cancer progression CD95 is frequently downregulated, raising the possibility that loss of CD95 is part of a mechanism for tumor evasion. However, CD95 engagement was reported to accelerate normal liver regeneration following partial hepatectomy. Additional evidence showed that induction of CD95 signaling in neuronal stem cells (NSCs) did not cause death but rather increased the survival of NSCs, while deletion of CD95 resulted in reduced neurogenesis. Furthermore, cancer patients frequently have elevated levels of the physiological ligand for CD95, CD95L. The author has demonstrated that CD95 has a growth-promoting role during tumorigenesis. Therefore, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD95R/L elimination (DICE). DICE is a necrotic form of mitotic catastrophe characterized by cell swelling and reactive oxygen species production followed by DNA damage, activation of caspase-2 and loss of mitochondrial outer membrane potential. As mentioned the role of CD95 in NSCs, and based on the link between CD95 signaling and the differentiation stage of caner. Whether DICE may differentially affect cancer cells depending on their differentiation status, that is, cancer stem cells (CSCs) versus more differentiated or normal cancer cells (non-CSCs). The author showed that stimulation of CD95 on multiple kinds of tumor cells induces a conversion from non- CSCs to CSCs with a concomitant reduction in sensitivity to CD95-mediated apoptosis and increased susceptibility to DICE. Induction of DICE in both cell lines and primary cancer cells resulted in a depletion of CSCs. These results showed that the two death mechanisms, DICE and CD95- mediated apoptosis, have opposing roles in eliminating CSCs and non-CSCs. As a consequence, the induction of both DICE and CD95-mediated apoptosis kills cancer cells more effectively than either mechanism alone.


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