在抗癌治疗的发展范围中内质网应激驱动下非折叠蛋白反应的分子开关重编程

Title:Reprogramming of Molecular Switching Events in UPR Driven ER Stress: Scope for Development of Anticancer Therapeutics

Volume: 16 Issue: 8

Author(s): B. Rah, D. Nayak, R. Rasool, S. Chakraborty, A. Katoch, H. Amin, A. Goswami

Affiliation:

关键词: 内质网应激；非折叠蛋白反应；分子开关；葡萄糖调节蛋白78；蛋白激酶样内质网激酶；治疗研究发展

摘要: The incitement of unfolded protein response (UPR) during endoplasmic reticulum (ER) stress by diverse intracellular (hypoxia, nutrient deprivation, etc.) or extracellular (environmental or drug induced) stimuli is considered a major threat for perturbing cellular homeostasis leading to the aggregation of unfolded proteins inside the cell. The catastrophic UPR events emerge as a prime cellular adaptation by remodeling cancer cell signaling and restoring ER homeostasis in favor of tumor growth. The transient ER stress protects cancer cells from undergoing apoptosis, whereas the prolonged stress response further activates many cell death pathways. The present review summarizes the UPR mediated triggering of transcriptional and translational reprogramming, which will provide novel therapeutic strategies towards pro-death mechanisms rather than a cellular adaptation in tumorigenesis. Nonetheless, the current topic also points out the reprogramming of emerging molecular switching events by complex UPR-mediated signaling to trigger apoptosis. The novel agents from various natural, semi-synthetic and synthetic sources that target ER stress signaling pathway to modulate selectively the UPR phenomena with preclinical efficacy are outlined. Since major emphasis on ER stress-induced transcriptional and translational reprogramming remains to be explored, we believe that the current subject will instigate more attention from the biomedical researchers in this certain research direction.

Cite this article as:

B. Rah, D. Nayak, R. Rasool, S. Chakraborty, A. Katoch, H. Amin, A. Goswami , Reprogramming of Molecular Switching Events in UPR Driven ER Stress: Scope for Development of Anticancer Therapeutics, Current Molecular Medicine 2016; 16 (8) . https://dx.doi.org/10.2174/1566524016666160829152658