targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer针对沉默延长因子2的激酶抑制增长和糖分会让阿霉素在肿瘤原位乳腺癌模型.pdf

Targeted Silencing of Elongation Factor 2 Kinase Suppresses Growth and Sensitizes Tumors to Doxorubicin in an Orthotopic Model of Breast Cancer 1 1 2 1 3 Ibrahim Tekedereli , S. Neslihan Alpay , Clint D. J. Tavares , Zehra E. Cobanoglu , Tamer S. Kaoud , Ibrahim Sahin1, Anil K. Sood4,5,6, Gabriel Lopez-Berestein1,5,6, Kevin N. Dalby2,3*, Bulent Ozpolat1,6* 1 Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 2 Graduate Program in Cell and Molecular Biology, The University of Texas, Austin, Texas, United States of America, 3 Division of Medicinal Chemistry, College of Pharmacy, The University of Texas, Austin, Texas, United States of America, 4 Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 5 Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 6 Center for RNAi and Non-Coding RNA, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America Abstract Eukaryotic elongation factor 2 kinase (eEF-2K), through its phosphorylation of elongation factor 2 (eEF2), provides a mechanism by which cells can control the rate of the elongation phase of protein synthesis. The activity of eEF-2K is increased in rapidly proliferating malignant cells, is inhibited during mitosis, and may contribute to the promotion of autophagy in response to anti-cancer therapies. The purpose of this study was to examine the therapeutic potential of targeting eEF-2K in