New Insights into the Unfolded Protein Response in Stem Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jun 16

PMID 27304053

Citations 18

Authors

Yanzhou Yang

Hoi Hung Cheung

Jiajie Tu

Kai Kei Miu

Wai Yee Chan

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Intravenous administration of muse cells improves cerebral ischemia outcome via immunomodulation in the spleen.

Kato Y, Aburakawa D, Tashiro R, Zhou Y, Rashad S, Endo H J Cereb Blood Flow Metab. 2024; 45(3):542-557.

PMID: 39397400 PMC: 11563515. DOI: 10.1177/0271678X241290363.

Matching queried single-cell open-chromatin profiles to large pools of single-cell transcriptomes and epigenomes for reference supported analysis.

Mishra S, Pandey N, Chawla S, Sharma M, Chandra O, Jha I Genome Res. 2023; 33(2):218-231.

PMID: 36653120 PMC: 10069468. DOI: 10.1101/gr.277015.122.

The vulnerable primed cancer stem cells in disguise: demystifying the role of Maspin.

Sheng S, Bernardo M, Dzinic S, Chen K, Sakr W Cancer Metastasis Rev. 2022; 41(4):965-974.

PMID: 36451067 PMC: 9713111. DOI: 10.1007/s10555-022-10070-2.

Systemic and local effect of the Drosophila headcase gene and its role in stress protection of Adult Progenitor Cells.

Giannios P, Casanova J PLoS Genet. 2021; 17(2):e1009362.

PMID: 33556132 PMC: 7895379. DOI: 10.1371/journal.pgen.1009362.

The mitochondria regulation of stem cell aging.

Wan Y, Finkel T Mech Ageing Dev. 2020; 191:111334.

PMID: 32818514 PMC: 7541753. DOI: 10.1016/j.mad.2020.111334.

References

Lu J, Dong H, Lin L, Wang Q, Huang L, Tan J . [Palmitate induces apoptosis and endoplasmic reticulum stress in human umbilical cord-derived mesenchymal stem cells]. Sheng Li Xue Bao. 2013; 65(6):600-6. View

Wang N, Wang Z, Peng C, You J, Shen J, Han S . Dietary compound isoliquiritigenin targets GRP78 to chemosensitize breast cancer stem cells via β-catenin/ABCG2 signaling. Carcinogenesis. 2014; 35(11):2544-54. DOI: 10.1093/carcin/bgu187. View

Chiu C, Lee L, Li Y, Chen Y, Lu Y, Li Y . Grp78 as a therapeutic target for refractory head-neck cancer with CD24(-)CD44(+) stemness phenotype. Cancer Gene Ther. 2013; 20(11):606-15. DOI: 10.1038/cgt.2013.64. View

Amici A, Onikoyi F, Bonfanti P . Lineage potential, plasticity and environmental reprogramming of epithelial stem/progenitor cells. Biochem Soc Trans. 2014; 42(3):637-44. DOI: 10.1042/BST20140047. View

Lu J, Wang Q, Huang L, Dong H, Lin L, Lin N . Palmitate causes endoplasmic reticulum stress and apoptosis in human mesenchymal stem cells: prevention by AMPK activator. Endocrinology. 2012; 153(11):5275-84. DOI: 10.1210/en.2012-1418. View

Rodolfo C, Di Bartolomeo S, Cecconi F . Autophagy in stem and progenitor cells. Cell Mol Life Sci. 2015; 73(3):475-96. PMC: 11108450. DOI: 10.1007/s00018-015-2071-3. View

Doupe D, Alcolea M, Roshan A, Zhang G, Klein A, Simons B . A single progenitor population switches behavior to maintain and repair esophageal epithelium. Science. 2012; 337(6098):1091-3. PMC: 3527005. DOI: 10.1126/science.1218835. View

Alter J, Bengal E . Stress-induced C/EBP homology protein (CHOP) represses MyoD transcription to delay myoblast differentiation. PLoS One. 2012; 6(12):e29498. PMC: 3248460. DOI: 10.1371/journal.pone.0029498. View

Cai Y, Pi W, Sivaprakasam S, Zhu X, Zhang M, Chen J . UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development. PLoS Genet. 2015; 11(11):e1005643. PMC: 4636156. DOI: 10.1371/journal.pgen.1005643. View

10.

Heijmans J, van Lidth de Jeude J, Koo B, Rosekrans S, Wielenga M, van de Wetering M . ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response. Cell Rep. 2013; 3(4):1128-39. DOI: 10.1016/j.celrep.2013.02.031. View

11.

Mohrin M, Shin J, Liu Y, Brown K, Luo H, Xi Y . Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging. Science. 2015; 347(6228):1374-7. PMC: 4447312. DOI: 10.1126/science.aaa2361. View

12.

Wielenga M, Colak S, Heijmans J, van Lidth de Jeude J, Rodermond H, Paton J . ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy. Cell Rep. 2015; 13(3):489-494. DOI: 10.1016/j.celrep.2015.09.016. View

13.

Guneta V, Loh Q, Choong C . Cell-secreted extracellular matrix formation and differentiation of adipose-derived stem cells in 3D alginate scaffolds with tunable properties. J Biomed Mater Res A. 2016; 104(5):1090-101. DOI: 10.1002/jbm.a.35644. View

14.

Cattaneo M, Baronchelli S, Schiffer D, Mellai M, Caldera V, Saccani G . Down-modulation of SEL1L, an unfolded protein response and endoplasmic reticulum-associated degradation protein, sensitizes glioma stem cells to the cytotoxic effect of valproic acid. J Biol Chem. 2013; 289(5):2826-38. PMC: 3908415. DOI: 10.1074/jbc.M113.527754. View

15.

Kharabi Masouleh B, Chevet E, Panse J, Jost E, ODwyer M, Bruemmendorf T . Drugging the unfolded protein response in acute leukemias. J Hematol Oncol. 2015; 8:87. PMC: 4504168. DOI: 10.1186/s13045-015-0184-7. View

16.

Yuzefovych L, Musiyenko S, Wilson G, Rachek L . Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS One. 2013; 8(1):e54059. PMC: 3546973. DOI: 10.1371/journal.pone.0054059. View

17.

Han J, Murthy R, Wood B, Song B, Wang S, Sun B . ER stress signalling through eIF2α and CHOP, but not IRE1α, attenuates adipogenesis in mice. Diabetologia. 2013; 56(4):911-24. PMC: 3606029. DOI: 10.1007/s00125-012-2809-5. View

18.

Chen G, Xu X, Zhang L, Fu Y, Wang M, Gu H . Blocking autocrine VEGF signaling by sunitinib, an anti-cancer drug, promotes embryonic stem cell self-renewal and somatic cell reprogramming. Cell Res. 2014; 24(9):1121-36. PMC: 4152737. DOI: 10.1038/cr.2014.112. View

19.

Michalak M, Gye M . Endoplasmic reticulum stress in periimplantation embryos. Clin Exp Reprod Med. 2015; 42(1):1-7. PMC: 4390675. DOI: 10.5653/cerm.2015.42.1.1. View

20.

Rossi D, Jamieson C, Weissman I . Stems cells and the pathways to aging and cancer. Cell. 2008; 132(4):681-96. DOI: 10.1016/j.cell.2008.01.036. View