New insights into the unfolded protein response in stem cells

Yanzhou Yang _, Hoi Hung Cheung, JiaJie Tu, Kai Kei Miu and Wai Yee Chan

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Oncotarget. 2016; 7:54010-54027. https://doi.org/10.18632/oncotarget.9833

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Yanzhou Yang1,2, Hoi Hung Cheung2, JiaJie Tu2, Kai Kei Miu2 and Wai Yee Chan2

1 Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, Ningxia Medical University, Yinchuan, Ningxia, P.R. China

2 The Chinese University of Hong Kong–Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, HKSAR, China

Correspondence to:

Yanzhou Yang, email:

Wai Yee Chan, email:

Keywords: endoplasmic reticulum stress, unfolded protein response, stem cells, differentiation, self-renewal

Received: March 29, 2016 Accepted: May 29, 2016 Published: June 06, 2016


The unfolded protein response (UPR) is an evolutionarily conserved adaptive mechanism to increase cell survival under endoplasmic reticulum (ER) stress conditions. The UPR is critical for maintaining cell homeostasis under physiological and pathological conditions. The vital functions of the UPR in development, metabolism and immunity have been demonstrated in several cell types. UPR dysfunction activates a variety of pathologies, including cancer, inflammation, neurodegenerative disease, metabolic disease and immune disease. Stem cells with the special ability to self-renew and differentiate into various somatic cells have been demonstrated to be present in multiple tissues. These cells are involved in development, tissue renewal and certain disease processes. Although the role and regulation of the UPR in somatic cells has been widely reported, the function of the UPR in stem cells is not fully known, and the roles and functions of the UPR are dependent on the stem cell type. Therefore, in this article, the potential significances of the UPR in stem cells, including embryonic stem cells, tissue stem cells, cancer stem cells and induced pluripotent cells, are comprehensively reviewed. This review aims to provide novel insights regarding the mechanisms associated with stem cell differentiation and cancer pathology.

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