Oncogenic Ras in tumour progression and metastasis

被引:222
作者
Giehl, K [1 ]
机构
[1] Univ Ulm, Dept Pharmacol & Toxicol, D-89069 Ulm, Germany
关键词
extracellular signal-regulated kinase (ERK); migration; phosphatidylinositol 3-kinase (PI3-K); Rho GTPases; signal transduction; transformation;
D O I
10.1515/BC.2005.025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The ras genes give rise to a family of related GTP-binding proteins that exhibit potent transforming potential. Mutational activation of Ras proteins promotes oncogenesis by disturbing a multitude of cellular processes, such as gene expression, cell cycle progression and cell proliferation, as well as cell survival, and cell migration. Ras signalling pathways are well known for their involvement in tumour initiation, but less is known about their contribution to invasion and metastasis. This review summarises the role and mechanisms of Ras signalling, especially the role of the Ras effector cascade Raf/MEK/ ERK, as well as the phosphatidylinositol 3-kinase/Akt pathway in Ras-mediated transformation and tumour progression. In addition, it discusses the impact of Rho GTPases on Ras-mediated transformation and metastasis.
引用
收藏
页码:193 / 205
页数:13
相关论文
共 172 条
[31]  
CARBONE A, 1991, ONCOGENE, V6, P731
[32]   Regulation of cell death protease caspase-9 by phosphorylation [J].
Cardone, MH ;
Roy, N ;
Stennicke, HR ;
Salvesen, GS ;
Franke, TF ;
Stanbridge, E ;
Frisch, S ;
Reed, JC .
SCIENCE, 1998, 282 (5392) :1318-1321
[33]   GEFs: structural basis for their activation of small GTP-binding proteins [J].
Cherfils, J ;
Chardin, P .
TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (08) :306-311
[34]   Essential role for oncogenic Ras in tumour maintenance [J].
Chin, L ;
Tam, A ;
Pomerantz, J ;
Wong, M ;
Holash, J ;
Bardeesy, N ;
Shen, Q ;
O'Hagan, R ;
Pantginis, J ;
Zhou, H ;
Horner, JW ;
Cordon-Cardo, C ;
Yancopoulos, GD ;
DePinho, RA .
NATURE, 1999, 400 (6743) :468-472
[35]   Ras signalling on the endoplasmic reticulum and the Golgi [J].
Chiu, VK ;
Bivona, T ;
Hach, A ;
Sajous, JB ;
Silletti, J ;
Wiener, H ;
Johnson, RL ;
Cox, AD ;
Philips, MR .
NATURE CELL BIOLOGY, 2002, 4 (05) :343-350
[36]   Mechanisms of regulating the Raf kinase family [J].
Chong, H ;
Vikis, HG ;
Guan, KL .
CELLULAR SIGNALLING, 2003, 15 (05) :463-469
[37]   Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Rac1 [J].
Clerk, A ;
Pham, FH ;
Fuller, SJ ;
Sahai, E ;
Aktories, K ;
Marais, R ;
Marshall, C ;
Sugden, PH .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (04) :1173-1184
[38]   PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway [J].
Coles, LC ;
Shaw, PE .
ONCOGENE, 2002, 21 (14) :2236-2244
[39]   Cellular survival: a play in three Akts [J].
Datta, SR ;
Brunet, A ;
Greenberg, ME .
GENES & DEVELOPMENT, 1999, 13 (22) :2905-2927
[40]   Mutations of the BRAF gene in human cancer [J].
Davies, H ;
Bignell, GR ;
Cox, C ;
Stephens, P ;
Edkins, S ;
Clegg, S ;
Teague, J ;
Woffendin, H ;
Garnett, MJ ;
Bottomley, W ;
Davis, N ;
Dicks, N ;
Ewing, R ;
Floyd, Y ;
Gray, K ;
Hall, S ;
Hawes, R ;
Hughes, J ;
Kosmidou, V ;
Menzies, A ;
Mould, C ;
Parker, A ;
Stevens, C ;
Watt, S ;
Hooper, S ;
Wilson, R ;
Jayatilake, H ;
Gusterson, BA ;
Cooper, C ;
Shipley, J ;
Hargrave, D ;
Pritchard-Jones, K ;
Maitland, N ;
Chenevix-Trench, G ;
Riggins, GJ ;
Bigner, DD ;
Palmieri, G ;
Cossu, A ;
Flanagan, A ;
Nicholson, A ;
Ho, JWC ;
Leung, SY ;
Yuen, ST ;
Weber, BL ;
Siegler, HF ;
Darrow, TL ;
Paterson, H ;
Marais, R ;
Marshall, CJ ;
Wooster, R .
NATURE, 2002, 417 (6892) :949-954