Combined inhibition of heat shock proteins 90 and 70 leads to simultaneous degradation of the oncogenic signaling proteins involved in muscle invasive bladder cancer
作者： Alice Cavanaugh , Brendon Juengst , Kathleen Sheridan , John F. Danella , Heinric Williams
关键词:
摘要: Heat shock protein 90 (HSP90) plays a critical role in the survival of cancer cells including muscle invasive bladder (MIBC). The addiction tumor to HSP90 has promoted development numerous inhibitors and their use clinical trials. This study evaluated inhibiting using STA9090 (STA) alone or combination with HSP70 inhibitor VER155008 (VER) several human MIBC cell lines. While both STA VER inhibited growth migration apoptosis, therapy was more effective. Therefore, signaling pathways involved were systematically interrogated following and/or treatments. not reduced expression proteins p53/Rb, PI3K SWI/SWF pathways. Interestingly, as effective degrading histone modification pathway such KDM6A (demethylase) EP300 (acetyltransferase) predicted by Cancer Genome Atlas (TCGA) data. data suggests that dual inhibition can simultaneously disrupt key MIBC.
impactjournals.com参考文章(55)
Abbey D. Zuehlke, Kristin Beebe, Len Neckers, Thomas Prince, Regulation and function of the human HSP90AA1 gene. Gene. ,vol. 570, pp. 8- 16 ,(2015) , 10.1016/J.GENE.2015.06.018
Thierry Lebret, R. William G. Watson, Vincent Molinié, Amanda O'Neill, Christophe Gabriel, John M. Fitzpatrick, Henry Botto, Heat Shock Proteins HSP27, HSP60, HSP70, and HSP90: Expression in Bladder Carcinoma Cancer. ,vol. 98, pp. 970- 977 ,(2003) , 10.1002/CNCR.11594
GULSUM OZLEM ELPEK, SEYDA KARAVELI, TAYYUP SIMSEK, NURAN KELES, NAZIF HIKMET AKSOY, Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries. Apmis. ,vol. 111, pp. 523- 530 ,(2003) , 10.1034/J.1600-0463.2003.1110411.X
Erik R. P. Zuiderweg, Eric B. Bertelsen, Aikaterini Rousaki, Matthias P. Mayer, Jason E. Gestwicki, Atta Ahmad, Allostery in the Hsp70 chaperone proteins. Topics in Current Chemistry. ,vol. 328, pp. 99- 153 ,(2012) , 10.1007/128_2012_323
Swee Sharp, Paul Workman, Inhibitors of the HSP90 molecular chaperone: current status. Advances in Cancer Research. ,vol. 95, pp. 323- 348 ,(2006) , 10.1016/S0065-230X(06)95009-X
Marc A Dall’Era, Liang Cheng, Chong-Xian Pan, Contemporary management of muscle-invasive bladder cancer. Expert Review of Anticancer Therapy. ,vol. 12, pp. 941- 950 ,(2012) , 10.1586/ERA.12.60
Woonyoung Choi, Bogdan Czerniak, Andrea Ochoa, Xiaoping Su, Arlene Siefker-Radtke, Colin Dinney, David J. McConkey, Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer Nature Reviews Urology. ,vol. 11, pp. 400- 410 ,(2014) , 10.1038/NRUROL.2014.129
C Giacinti, A Giordano, RB and cell cycle progression Oncogene. ,vol. 25, pp. 5220- 5227 ,(2006) , 10.1038/SJ.ONC.1209615
Vasily V Ogryzko, R.Louis Schiltz, Valya Russanova, Bruce H Howard, Yoshihiro Nakatani, The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases Cell. ,vol. 87, pp. 953- 959 ,(1996) , 10.1016/S0092-8674(00)82001-2
David M. Roy, Logan A. Walsh, Timothy A. Chan, Driver mutations of cancer epigenomes Protein & Cell. ,vol. 5, pp. 265- 296 ,(2014) , 10.1007/S13238-014-0031-6