Calpain activity is generally elevated during transformation but has oncogene-specific biological functions

被引:65
作者
Carragher, NO
Fonseca, BD
Frame, MC
机构
[1] Canc Res UK Beatson Labs, Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland
[2] Univ Glasgow, Inst Biol & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
来源
NEOPLASIA | 2004年 / 6卷 / 01期
关键词
calpain; oncogene; focal adhesion; migration; apoptosis;
D O I
10.1016/S1476-5586(04)80053-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Several oncogene and tumor-suppressor gene products are known substrates for the calpain family of cysteine proteases, and calpain is required for transformation by v-src and tumor invasion. Thus, we have now addressed whether calpain is generally associated with transformation and how calpain contributes to oncogene function. Our results demonstrate that calpain activity is enhanced upon transformation induced by the v-Src, v-Jun, v-Myc, k-Ras, and v-Fos oncoproteins. Furthermore, elevated calpain activity commonly promotes focal adhesion remodelling, disruption of actin cytoskeleton, morphological transformation, and cell migration, although proteolysis of target substrates (such as focal adhesion kinase, talin, and spectrin) is differently specified by individual oncoproteins. Interestingly, v-Fos differs from other common oncoproteins in not requiring calpain activity for actin/adhesion remodelling or migration of v-Fos transformed cells. However, anchorage-independent growth of all transformed cells is sensitive to calpain inhibition. In addition, elevated calpain activity contributes to oncogene-induced apoptosis associated with transformation by v-Myc. Taken together, these studies demonstrate that calpain activity is necessary for full cellular transformation induced by common oncoproteins, but has distinct roles in oncogenic events induced by individual transforming proteins. Thus, targeting calpain activity may represent a useful general strategy for interfering with activated proto-oncogenes in cancer cells.
引用
收藏
页码:53 / 73
页数:21
相关论文
共 84 条
[1]   Investigation of the interaction of m-calpain with phospholipids: Calpain-phospholipid interactions [J].
Arthur, JSC ;
Crawford, C .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1996, 1293 (02) :201-206
[2]  
Atencio IA, 2000, CELL GROWTH DIFFER, V11, P247
[3]   Phosphorylation of rat brain calpastatins by protein kinase C [J].
Averna, M ;
De Tullio, R ;
Salamino, F ;
Melloni, E ;
Pontremoli, S .
FEBS LETTERS, 1999, 450 (1-2) :13-16
[4]   COLOCALIZATION OF CALCIUM-DEPENDENT PROTEASE-II AND ONE OF ITS SUBSTRATES AT SITES OF CELL-ADHESION [J].
BECKERLE, MC ;
BURRIDGE, K ;
DEMARTINO, GN ;
CROALL, DE .
CELL, 1987, 51 (04) :569-577
[5]  
BENNETT V, 1993, ANNU REV CELL BIOL, V9, P27, DOI 10.1146/annurev.cb.09.110193.000331
[6]  
Bhatt A, 2002, J CELL SCI, V115, P3415
[7]   Src-mediated tyrosine phosphorylation of NR2 subunits of N-methyl-D-aspartate receptors protects from calpain-mediated truncation of their C-terminal domains [J].
Bi, RF ;
Rong, YQ ;
Bernard, A ;
Khrestchatisky, M ;
Baudry, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (34) :26477-26483
[8]   Evidence that β3 integrin-induced Rac activation involves the calpain-dependent formation of integrin clusters that are distinct from the focal complexes and focal adhesions that form as Rac and RhoA become active [J].
Bialkowska, K ;
Kulkarni, S ;
Du, XP ;
Goll, DE ;
Saido, TC ;
Fox, JEB .
JOURNAL OF CELL BIOLOGY, 2000, 151 (03) :685-695
[9]  
Braun C, 1999, INT J CANCER, V84, P6, DOI 10.1002/(SICI)1097-0215(19990219)84:1<6::AID-IJC2>3.3.CO
[10]  
2-K