tailieunhanh - Báo cáo y học: "Unfolded protein response in cancer: the Physician’s perspective"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Unfolded protein response in cancer: the Physician’s perspective. | Li et al. Journal of Hematology Oncology 2011 4 8 http content 4 1 8 REVIEW JOURNAL OF HEMATOLOGY ONCOLOGY Open Access Unfolded protein response in cancer the Physician s perspective Xuemei Li1 Kezhong Zhang2 Zihai Li3 Abstract The unfolded protein response UPR is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum ER . Cancer cells are often exposed to hypoxia nutrient starvation oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials. 1. The unfolded protein response mechanism During tumorigenesis the high proliferation rate of cancer cells requires increased activities of ER machinery in facilitating protein folding assembly and transport. Other pathologic stimuli can interrupt the protein folding process and subsequently cause accumulation of unfolded or misfolded proteins in the ER a condition referred to as ER stress 1-5 . These pathologic stimuli include those that cause ER calcium depletion altered glycosylation nutrient deprivation oxidative stress DNA damage or energy perturbation or fluctuations. In order to handle the accumulation of the unfolded or misfolded proteins the ER evolves a group of signal transduction pathways collectively termed the unfolded protein response UPR to alter transcriptional and translational programs to maintain ER homeostasis 6-8 . UPR has two primary functions 1 .