Urokinase-type plasminogen activator receptor regulates apoptotic sensitivity of colon cancer HCT116 cell line to TRAIL via JNK-p53 pathway

作者: Kai Wang , Ping-Kun Zhou , Yao Wang , Zi-Chun Hua , Xiufeng Liu

DOI: 10.1007/S10495-014-1025-9

关键词:

摘要: The urokinase-type plasminogen activator receptor (uPAR) serves not only as an anchor for but also participates in intracellular signal transduction events. In this study, we investigated whether uPAR could modulate TRAIL-induced apoptosis human colon cancer cells HCT116. Using antisense strategy, established a stable HCT116 cell line with down-regulated uPAR. sensitivity to was evaluated by FACS analysis. Our results show that the inhibition of sensitize apoptosis. changed expression mitochondrial apoptotic pathway proteins, including Bcl-2, Bax, Bid and p53, pro-apoptotic manner. We found phosphorylation FAK, ERK JNK. p53 RNA interference rescued from enhanced apoptosis, thus indicating is critical enhancing Furthermore, JNK, ERK, involved up-regulation p53. JNK negatively regulated protein level. Overall, our can via active pathways involved.

参考文章(56)
Heike Allgayer, Alexander Marx, Mukesh Gandhari, Norbert Arens, Ralf Hildenbrand, Philipp Stroebel, The urokinase-system--role of cell proliferation and apoptosis. Histology and Histopathology. ,vol. 23, pp. 227- 236 ,(2008) , 10.14670/HH-23.227
Yoshihide Tsujimoto, Bcl-2 family of proteins: life-or-death switch in mitochondria. Bioscience Reports. ,vol. 22, pp. 47- 58 ,(2002) , 10.1023/A:1016061006256
Anning Lin, Benjamin Dibling, The true face of JNK activation in apoptosis. Aging Cell. ,vol. 1, pp. 112- 116 ,(2002) , 10.1046/J.1474-9728.2002.00014.X
Sai MuraliKrishna Pulukuri, Christopher S. Gondi, Sajani S. Lakka, Aman Jutla, Norman Estes, Meena Gujrati, Jasti S. Rao, RNA Interference-directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity in Vivo Journal of Biological Chemistry. ,vol. 280, pp. 36529- 36540 ,(2005) , 10.1074/JBC.M503111200
Jerry E Chipuk, Tomomi Kuwana, Lisa Bouchier-Hayes, Nathalie M Droin, Donald D Newmeyer, Martin Schuler, Douglas R Green, None, Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. ,vol. 303, pp. 1010- 1014 ,(2004) , 10.1126/SCIENCE.1092734
Guido Kroemer, Lorenzo Galluzzi, Catherine Brenner, Mitochondrial Membrane Permeabilization in Cell Death Physiological Reviews. ,vol. 87, pp. 99- 163 ,(2007) , 10.1152/PHYSREV.00013.2006
Seoung Woo Shin, Jeen-Woo Park, Ursolic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis. Biochimica et Biophysica Acta. ,vol. 1833, pp. 723- 730 ,(2013) , 10.1016/J.BBAMCR.2012.12.005
R Besch, C Berking, C Kammerbauer, K Degitz, Inhibition of urokinase-type plasminogen activator receptor induces apoptosis in melanoma cells by activation of p53. Cell Death & Differentiation. ,vol. 14, pp. 818- 829 ,(2007) , 10.1038/SJ.CDD.4402065
Gerald W. Prager, Johannes M. Breuss, Stefan Steurer, Damla Olcaydu, Judit Mihaly, Patrick M. Brunner, Hannes Stockinger, Bernd R. Binder, Vascular Endothelial Growth Factor Receptor-2–Induced Initial Endothelial Cell Migration Depends on the Presence of the Urokinase Receptor Circulation Research. ,vol. 94, pp. 1562- 1570 ,(2004) , 10.1161/01.RES.0000131498.36194.6B