The paradox of the unfolded protein response in cancer.
The endoplasmic reticulum (ER) is an elaborate organelle that is essential for cellular function and survival. Conditions that interfere with ER functioning can lead to the accumulation of unfolded proteins, which are detected by transmembrane sensors that then initiate the unfolded protein response (UPR) to restore ER proteostasis. If the adaptive response fails, apoptotic cell death ensues. Many studies have focused on how this failure initiates apoptosis, particularly because ER stress-induced apoptosis is implicated in the pathophysiology of several diseases, including cancer. Whether the UPR inhibits tumour growth or protects tumour cells by facilitating their adaptation to stressful conditions within the tumour microenvironment is unknown, and dissection of the UPR network will likely provide answers to this question. In this review, we aim to elucidate the paradoxical role of the UPR in apoptosis and cancer.
Department of Hepatology and Gastroenterology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. hans.vanvlierberghe@ugent.be.
Yves-Paul
YP
Vandewynckel
Debby
D
Laukens
Anja
A
Geerts
Eliene
E
Bogaerts
Annelies
A
Paridaens
Xavier
X
Verhelst
Sophie
S
Janssens
Femke
F
Heindryckx
Hans
H
Van Vlierberghe
D000818:Animals; D017209:Apoptosis; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D056811:Unfolded Protein Response
D009363:Neoplasm Proteins
Cancer; PERK kinase; activating transcription factor 6; endoplasmic reticulum; inositol requiring enzyme-1; molecular chaperones; review; stress; unfolded protein response