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 and A. Goswami
Affiliation:
Keywords:
ER stress, UPR, molecular switching, GRP78, PERK, therapeutic development.
Abstract: 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.
