PMID- 16627981
OWN - NLM
STAT- MEDLINE
DCOM- 20070129
LR  - 20200930
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 5
IP  - 6
DP  - 2006 Jun
TI  - Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by 
      suppression of NF-kappaB survival signaling in hepatocellular carcinoma.
PG  - 615-22
AB  - CYLD is a tumor suppressor gene related to cylindroma and is negative regulator 
      of NF-kappaB. However, antitumor effect of CYLD has not been reported. The 
      activation of NF-kappaB induced by tumor necrosis factor-related 
      apoptosis-inducing ligand (TRAIL) renders hepatocellular carcinoma (HCC) 
      resistant to TRAIL-mediated cell apoptosis. Here we described that the adenoviral 
      vector expressing CYLD (Ad/hTERT-CYLD) augmented the cytotoxicity of TRAIL in HCC 
      cells by negatively regulating NF-kappaB activity since CYLD could reverse the 
      ubiquitination of TNF receptor-associated factor 2 (TRAF2) and interact with the 
      IkappaB kinasegamma (IKKgamma). The combined treatment of Ad/hTERT-CYLD and a 
      conditionally replicating adenovirus carrying TRAIL gene (ZD55-TRAIL) induced 
      rapid and potent apoptosis in HCC cells, characterized by activation of 
      caspase-3, caspase-8, PARP and the reduction of X-linked inhibitor of apoptosis 
      protein (XIAP). In animal study, the combined treatment could eradicate the 
      BEL7404 xenograft tumors. In contrast, treatment with Ad/hTERT-CYLD or ZD55-TRAIL 
      alone achieved less antitumor effect. IN CONCLUSION: CYLD inhibits TRAIL-mediated 
      NF-kappaB activation and enhances the sensitivity of HCC cells to TRAIL-triggered 
      apoptosis. The combined delivery of Ad/hTERT-CYLD and ZD55-TRAIL may be a new 
      useful strategy for HCC or other tumor cells with enhanced NF-kappaB activity.
FAU - Chu, Liang
AU  - Chu L
AD  - Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological 
      Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of 
      Sciences, Shanghai, PR China.
FAU - Gu, Jinfa
AU  - Gu J
FAU - He, Zhongniu
AU  - He Z
FAU - Xiao, Tian
AU  - Xiao T
FAU - Liu, Xinyuan
AU  - Liu X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060605
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (NF-kappa B)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.4.19.12 (CYLD protein, human)
RN  - EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
SB  - IM
MH  - Adenoviridae
MH  - Carcinoma, Hepatocellular
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Deubiquitinating Enzyme CYLD
MH  - Genes, Tumor Suppressor
MH  - Genetic Vectors
MH  - Humans
MH  - Liver Neoplasms
MH  - NF-kappa B/antagonists & inhibitors/*physiology
MH  - Signal Transduction
MH  - TNF-Related Apoptosis-Inducing Ligand/*genetics
MH  - Tumor Suppressor Proteins/*genetics
EDAT- 2006/04/22 09:00
MHDA- 2007/01/30 09:00
CRDT- 2006/04/22 09:00
PHST- 2006/04/22 09:00 [pubmed]
PHST- 2007/01/30 09:00 [medline]
PHST- 2006/04/22 09:00 [entrez]
AID - 2662 [pii]
AID - 10.4161/cbt.5.6.2662 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2006 Jun;5(6):615-22. doi: 10.4161/cbt.5.6.2662. Epub 2006 Jun 
      5.