A tumor suppressor role for srGAP3 in mammary epithelial cells
作者： A Lahoz , A Hall
DOI: 10.1038/ONC.2012.489
关键词: Cell culture 、 Moesin 、 Biology 、 Ezrin 、 Phosphorylation 、 Cell biology 、 Radixin 、 RAC1 、 Kinase 、 Myosin light-chain kinase
摘要: srGAP3, a member of the Slit-Robo sub-family Rho GTPase-activating proteins (Rho GAPs), controls actin and microtubule dynamics through negative regulation Rac. Here, we describe potential role for srGAP3 as tumor suppressor in mammary epithelial cells. We show that RNAi-mediated depletion promotes Rac dependent, anchorage-independent growth partially transformed human cells (HMECs). Furthermore, expression is absent, or significantly reduced 7/10 breast cancer cell lines compared with normal HMECs. Re-expression subset these inhibits both invasion GAP-dependent manner, this accompanied by an increase phosphorylation ezrin/radixin/moesin (ERM) family myosin light chain 2 (MLC2). Inhibition regulated kinase, ROCK, reduces ERM MLC2 restores invasion. conclude has suppressor-like activity HMECs, likely its regulator Rac1.
nature.com
sci-hub.se 参考文章(38)
M Ikebe, D J Hartshorne, Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase. Journal of Biological Chemistry. ,vol. 260, pp. 10027- 10031 ,(1985) , 10.1016/S0021-9258(17)39206-2
Pontus Aspenström, Chapter 1 Roles of F-BAR/PCH Proteins in the Regulation of Membrane Dynamics and Actin Reorganization International Review of Cell and Molecular Biology. ,vol. 272, pp. 1- 31 ,(2008) , 10.1016/S1937-6448(08)01601-8
Paraic A. Kenny, Genee Y. Lee, Connie A. Myers, Richard M. Neve, Jeremy R. Semeiks, Paul T. Spellman, Katrin Lorenz, Eva H. Lee, Mary Helen Barcellos-Hoff, Ole W. Petersen, Joe W. Gray, Mina J. Bissell, The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression Molecular Oncology. ,vol. 1, pp. 84- 96 ,(2007) , 10.1016/J.MOLONC.2007.02.004
Victoria Sanz-Moreno, Gilles Gadea, Jessica Ahn, Hugh Paterson, Pierfrancesco Marra, Sophie Pinner, Erik Sahai, Christopher J Marshall, None, Rac Activation and Inactivation Control Plasticity of Tumor Cell Movement Cell. ,vol. 135, pp. 510- 523 ,(2008) , 10.1016/J.CELL.2008.09.043
Gerben C.M. Zondag, Eva E. Evers, Jean P. ten Klooster, Lennert Janssen, Rob A. van der Kammen, John G. Collard, Oncogenic Ras downregulates Rac activity, which leads to increased Rho activity and epithelial-mesenchymal transition Journal of Cell Biology. ,vol. 149, pp. 775- 782 ,(2000) , 10.1083/JCB.149.4.775
S. H. Soderling, E. S. Guire, S. Kaech, J. White, F. Zhang, K. Schutz, L. K. Langeberg, G. Banker, J. Raber, J. D. Scott, A WAVE-1 and WRP Signaling Complex Regulates Spine Density, Synaptic Plasticity, and Memory The Journal of Neuroscience. ,vol. 27, pp. 355- 365 ,(2007) , 10.1523/JNEUROSCI.3209-06.2006
Yongjing Guo, Pouya Pakneshan, Julienne Gladu, Andrew Slack, Moshe Szyf, Shafaat A Rabbani, None, Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion. Journal of Biological Chemistry. ,vol. 277, pp. 41571- 41579 ,(2002) , 10.1074/JBC.M201864200
Chengfeng Yang, Marcelo G. Kazanietz, Chimaerins: GAPs that bridge diacylglycerol signalling and the small G-protein Rac. Biochemical Journal. ,vol. 403, pp. 1- 12 ,(2007) , 10.1042/BJ20061750
Saskia I. J. Ellenbroek, John G. Collard, Rho GTPases: functions and association with cancer. Clinical & Experimental Metastasis. ,vol. 24, pp. 657- 672 ,(2007) , 10.1007/S10585-007-9119-1
Salwati Shuib, Dominic McMullan, Eleanor Rattenberry, Richard M. Barber, Fatimah Rahman, Malgosia Zatyka, Cyril Chapman, Fiona Macdonald, Farida Latif, Val Davison, Eamonn R. Maher, Microarray based analysis of 3p25-p26 deletions (3p- syndrome). American Journal of Medical Genetics Part A. ,vol. 149, pp. 2099- 2105 ,(2009) , 10.1002/AJMG.A.32824