Cell surface death receptor signaling in normal and cancer cells

被引:246
作者
Özören, N
El-Deiry, WS
机构
[1] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA
关键词
death receptors; extrinsic pathway; intrinsic pathway; TRAIL cancer therapy; death receptor mutations;
D O I
10.1016/S1044-579X(02)00131-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The extrinsic cell death pathway is initiated upon ligand-receptor interactions at the cell surface including FAS ligand-FAS/APO1, TNF-TNF receptors, and TRAIL-TRAIL receptors. Abnormalities of various components of these pathways have been identified in human cancer including loss of FAS expression, deletion or loss of TRAIL receptor DR4, mutation of TRAIL receptor DR5, overexpression of TRAIL decoy TRID or overexpression of Fas decoy, as well as overexpression of the caspase activation inhibitor, FLIP. Death ligands have been explored as potential therapeutics in cancer therapy with some limitations in the case of FAS and TNF due to toxicities. TRAIL remains promising as a therapeutic and has potential for combination with chemo- or radio-therapy. The death receptor signaling pathways include cross-talk with the mitochondrial pathway and can in some cases be influenced by mitochondrial membrane potential changes or NF-kappaB. FLIP and BCL-XL expression may reduce sensitivity of cancer cells to combination therapies. (C) 2003 Published by Elsevier Science Ltd.
引用
收藏
页码:135 / 147
页数:13
相关论文
共 145 条
[81]   LETHAL EFFECT OF THE ANTI-FAS ANTIBODY IN MICE [J].
OGASAWARA, J ;
WATANABEFUKUNAGA, R ;
ADACHI, M ;
MATSUZAWA, A ;
KASUGAI, T ;
KITAMURA, Y ;
ITOH, N ;
SUDA, T ;
NAGATA, S .
NATURE, 1993, 364 (6440) :806-809
[82]  
OWENSCHAUB LB, 1995, MOL CELL BIOL, V15, P3032
[83]  
Özören N, 2000, CANCER RES, V60, P6259
[84]  
Özören N, 2000, INT J ONCOL, V16, P917
[85]  
Pai SI, 1998, CANCER RES, V58, P3513
[86]   An antagonist decoy receptor and a death domain-containing receptor for TRAIL [J].
Pan, GH ;
Ni, J ;
Wei, YF ;
Yu, GL ;
Gentz, R ;
Dixit, VM .
SCIENCE, 1997, 277 (5327) :815-818
[87]   TRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL signalling [J].
Pan, GH ;
Ni, J ;
Yu, GL ;
Wei, YF ;
Dixit, VM .
FEBS LETTERS, 1998, 424 (1-2) :41-45
[88]   The receptor for the cytotoxic ligand TRAIL [J].
Pan, GH ;
ORourke, K ;
Chinnaiyan, AM ;
Gentz, R ;
Ebner, R ;
Ni, J ;
Dixit, VM .
SCIENCE, 1997, 276 (5309) :111-113
[89]   Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 and activation of procaspase-9 by heat shock protein 90 [J].
Pandey, P ;
Saleh, A ;
Nakazawa, A ;
Kumar, S ;
Srinivasula, SM ;
Kumar, V ;
Weichselbaum, R ;
Nalin, C ;
Alnemri, ES ;
Kufe, D ;
Kharbanda, S .
EMBO JOURNAL, 2000, 19 (16) :4310-4322
[90]   Inactivating mutations of KILLER/DR5 gene in gastric cancers [J].
Park, WS ;
Lee, JH ;
Shin, MS ;
Park, JY ;
Kim, HS ;
Kim, YS ;
Park, CH ;
Lee, SK ;
Lee, SH ;
Lee, SN ;
Kim, H ;
Yoo, NJ ;
Lee, JY .
GASTROENTEROLOGY, 2001, 121 (05) :1219-1225