Donavon C Hiss1, Gary A Gabriels. 1. Head, Molecular Oncology Research Programme University of the Western Cape, Department of Medical BioSciences, Bellville, 7535, South Africa +27 21 959 2334 ; +27 21 959 1563 ; dhiss@uwc.ac.za.
Abstract
BACKGROUND: In eukaryotes, endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are coordinately regulated to maintain steady-state levels and activities of various cellular proteins to ensure cell survival. OBJECTIVE: This review (Part I of II) focuses on specific ERS and UPR signalling regulators, their expression in the cancer phenotype and apoptosis, and proposes how their implication in these processes can be rationalised into proteasome inhibition, apoptosis induction and the development of more efficacious targeted molecular cancer therapies. METHOD: In this review, we contextualise many ERS and UPR client proteins that are deregulated or mutated in cancers and show links between ERS and the UPR, their implication in oncogenic transformation, tumour progression and escape from immune surveillance, apoptosis inhibition, angiogenesis, metastasis, acquired drug resistance and poor cancer prognosis. CONCLUSION: Evasion of programmed cell death or apoptosis is a hallmark of cancer that enables tumour cells to proliferate uncontrollably. Successful eradication of cancer cells through targeting ERS- and UPR-associated proteins to induce apoptosis is currently being pursued as a central tenet of anticancer drug discovery.
BACKGROUND: In eukaryotes, endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are coordinately regulated to maintain steady-state levels and activities of various cellular proteins to ensure cell survival. OBJECTIVE: This review (Part I of II) focuses on specific ERS and UPR signalling regulators, their expression in the cancer phenotype and apoptosis, and proposes how their implication in these processes can be rationalised into proteasome inhibition, apoptosis induction and the development of more efficacious targeted molecular cancer therapies. METHOD: In this review, we contextualise many ERS and UPR client proteins that are deregulated or mutated in cancers and show links between ERS and the UPR, their implication in oncogenic transformation, tumour progression and escape from immune surveillance, apoptosis inhibition, angiogenesis, metastasis, acquired drug resistance and poor cancer prognosis. CONCLUSION: Evasion of programmed cell death or apoptosis is a hallmark of cancer that enables tumour cells to proliferate uncontrollably. Successful eradication of cancer cells through targeting ERS- and UPR-associated proteins to induce apoptosis is currently being pursued as a central tenet of anticancer drug discovery.
Authors: Pooneh Mokarram; Mohammed Albokashy; Maryam Zarghooni; Mohammad Amin Moosavi; Zahra Sepehri; Qi Min Chen; Andrzej Hudecki; Aliyeh Sargazi; Javad Alizadeh; Adel Rezaei Moghadam; Mohammad Hashemi; Hesam Movassagh; Thomas Klonisch; Ali Akbar Owji; Marek J Łos; Saeid Ghavami Journal: Autophagy Date: 2017-02-23 Impact factor: 16.016