PMID- 32147543
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20200721
IS  - 1879-2561 (Electronic)
IS  - 0304-419X (Linking)
VI  - 1873
IP  - 2
DP  - 2020 Apr
TI  - Caspase-8: The double-edged sword.
PG  - 188357
LID - S0304-419X(19)30176-3 [pii]
LID - 10.1016/j.bbcan.2020.188357 [doi]
AB  - Caspase-8 is a cysteine - aspartate specific protease that classically triggers 
      the extrinsic apoptotic pathway, in response to the activation of cell surface 
      Death Receptors (DRs) like FAS, TRAIL-R and TNF-R. Besides it's roles in 
      triggering death receptor-mediated apoptosis, Caspase-8 has also been implicated 
      in the onsets of anoikis, autophagy and pyroptosis. Furthermore, Caspase-8 also 
      plays a crucial pro-survival function by inhibiting an alternative form of 
      programmed cell death called necroptosis. Low expression levels of pro-Caspase-8 
      is therefore associated with the malignant transformation of cancers. However, 
      the long-held notion that pro-Caspase-8 expression/activity is generally lost in 
      most cancers, thereby contributing to apoptotic escape and enhanced resistance to 
      anti-cancer therapeutics, has been found to be true for only a minority of 
      cancers types. In the majority of cases, pro-Caspase-8 expression is maintained 
      and sometimes elevated, while it's apoptotic activity is regulated through 
      different mechanisms. This supports the notion that the non-apoptotic functions 
      of Caspase-8 offer growth advantage in these cancer types and have, therefore, 
      gained renewed interest in the recent years. In light of these reasons, a number 
      of therapeutic approaches have been employed, with the intent of targeting 
      pro-Caspase-8 in cancer cells. In this review, we would attempt to discuss - the 
      classic roles of Caspase-8 in initiating apoptosis; it's non-apoptotic functions; 
      it's the clinical significance in different cancer types; and the therapeutic 
      applications exploiting the ability of pro-Caspase-8 to regulate various cellular 
      functions.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Mandal, Ranadip
AU  - Mandal R
AD  - Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany.
FAU - Barron, Joan Compte
AU  - Barron JC
AD  - Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany; Universitat 
      Autonoma de Barcelona, 119-129008035 Barcelona, Spain.
FAU - Kostova, Izabela
AU  - Kostova I
AD  - Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany.
FAU - Becker, Sven
AU  - Becker S
AD  - Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany.
FAU - Strebhardt, Klaus
AU  - Strebhardt K
AD  - Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany; German 
      Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: 
      strebhardt@em.uni-frankfurt.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200305
PL  - Netherlands
TA  - Biochim Biophys Acta Rev Cancer
JT  - Biochimica et biophysica acta. Reviews on cancer
JID - 9806362
RN  - 0 (Cytokines)
RN  - 0 (Inflammasomes)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Casp8 protein, mouse)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/immunology
MH  - Autophagy/genetics/immunology
MH  - Caspase 8/genetics/*metabolism
MH  - Cell Cycle/genetics
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Survival/genetics
MH  - Cytokines/immunology/metabolism
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Inflammasomes/immunology/metabolism
MH  - Mice
MH  - Necroptosis/genetics/immunology
MH  - Neoplasms/genetics/immunology/*pathology
MH  - Signal Transduction/genetics/immunology
MH  - Up-Regulation
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/03/10 06:00
MHDA- 2020/07/22 06:00
CRDT- 2020/03/10 06:00
PHST- 2019/12/02 00:00 [received]
PHST- 2020/02/13 00:00 [revised]
PHST- 2020/03/03 00:00 [accepted]
PHST- 2020/03/10 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2020/03/10 06:00 [entrez]
AID - S0304-419X(19)30176-3 [pii]
AID - 10.1016/j.bbcan.2020.188357 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188357. doi: 
      10.1016/j.bbcan.2020.188357. Epub 2020 Mar 5.