The Role of the Hypoxia-Related Unfolded Protein Response (UPR) in the Tumor Microenvironment

被引:17
作者
Bartoszewska, Sylwia [1 ]
Collawn, James F. [2 ]
Bartoszewski, Rafal [3 ]
机构
[1] Med Univ Gdansk, Dept Inorgan Chem, PL-80416 Gdansk, Poland
[2] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA
[3] Univ Wroclaw, Fac Biotechnol, Dept Biophys, F Joliot Curie 14a St, PL-50383 Wroclaw, Poland
关键词
ER-stress; hypoxia-reoxygenation injury; TME; cell fate determination; UPRmt; ENDOPLASMIC-RETICULUM STRESS; ISCHEMIA-REPERFUSION INJURY; MESSENGER-RNA TRANSLATION; INDUCIBLE FACTOR-1 HIF-1; DISULFIDE BOND FORMATION; FACTOR-A EXPRESSION; ER-STRESS; ENDOTHELIAL-CELLS; TRANSCRIPTION FACTOR; BREAST-CANCER;
D O I
10.3390/cancers14194870
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary The complex signaling networks that different cancers utilize for cell survival remain poorly understood. A major problem is the complexity of the tumor microenvironments (TME). Here, we discuss the role of intermittent hypoxia as one of the inducers of the UPR in the TME and the related implications of it for both cancer progression and therapeutic approaches. Despite our understanding of the unfolded protein response (UPR) pathways, the crosstalk between the UPR and the complex signaling networks that different cancers utilize for cell survival remains to be, in most cases, a difficult research barrier. A major problem is the constant variability of different cancer types and the different stages of cancer as well as the complexity of the tumor microenvironments (TME). This complexity often leads to apparently contradictory results. Furthermore, the majority of the studies that have been conducted have utilized two-dimensional in vitro cultures of cancer cells that were exposed to continuous hypoxia, and this approach may not mimic the dynamic and cyclic conditions that are found in solid tumors. Here, we discuss the role of intermittent hypoxia, one of inducers of the UPR in the cellular component of TME, and the way in which intermittent hypoxia induces high levels of reactive oxygen species, the activation of the UPR, and the way in which cancer cells modulate the UPR to aid in their survival. Although the past decade has resulted in defining the complex, novel non-coding RNA-based regulatory networks that modulate the means by which hypoxia influences the UPR, we are now just to beginning to understand some of the connections between hypoxia, the UPR, and the TME.
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页数:24
相关论文
共 335 条
[1]   Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses [J].
Adelman, DM ;
Gertsenstein, M ;
Nagy, A ;
Simon, MC ;
Maltepe, E .
GENES & DEVELOPMENT, 2000, 14 (24) :3191-3203
[2]   Oxidized Phospholipids Regulate Expression of ATF4 and VEGF in Endothelial Cells via NRF2-Dependent Mechanism: Novel Point of Convergence Between Electrophilic and Unfolded Protein Stress Pathways [J].
Afonyushkin, Taras ;
Oskolkova, Olga V. ;
Philippova, Maria ;
Resink, Therese J. ;
Erne, Paul ;
Binder, Bernd R. ;
Bochkov, Valery N. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2010, 30 (05) :1007-U275
[3]   Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer [J].
Almanza, Aitor ;
Mnich, Katarzyna ;
Blomme, Arnaud ;
Robinson, Claire M. ;
Rodriguez-Blanco, Giovanny ;
Kierszniowska, Sylwia ;
McGrath, Eoghan P. ;
Le Gallo, Matthieu ;
Pilalis, Eleftherios ;
Swinnen, Johannes, V ;
Chatziioannou, Aristotelis ;
Chevet, Eric ;
Gorman, Adrienne M. ;
Samali, Afshin .
NATURE COMMUNICATIONS, 2022, 13 (01)
[4]   Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications [J].
Almanza, Aitor ;
Carlesso, Antonio ;
Chintha, Chetan ;
Creedican, Stuart ;
Doultsinos, Dimitrios ;
Leuzzi, Brian ;
Luis, Andreia ;
McCarthy, Nicole ;
Montibeller, Luigi ;
More, Sanket ;
Papaioannou, Alexandra ;
Pueschel, Franziska ;
Sassano, Maria Livia ;
Skoko, Josip ;
Agostinis, Patrizia ;
de Belleroche, Jackie ;
Eriksson, Leif A. ;
Fulda, Simone ;
Gorman, Adrienne M. ;
Healy, Sandra ;
Kozlov, Andrey ;
Munoz-Pinedo, Cristina ;
Rehm, Markus ;
Chevet, Eric ;
Samali, Afshin .
FEBS JOURNAL, 2019, 286 (02) :241-278
[5]   Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients [J].
Almendros, Isaac ;
Angel Martinez-Garcia, Miguel ;
Campos-Rodriguez, Francisco ;
Riveiro-Falkenbach, Erica ;
Rodriguez-Peralto, Jose L. ;
Nagore, Eduardo ;
Martorell-Calatayud, Antonio ;
Hernandez Blasco, Luis ;
Banuls Roca, Jose ;
Chiner Vives, Eusebi ;
Sanchez-de-la-Torre, Alicia ;
Abad-Capa, Jorge ;
Maria Montserrat, Josep ;
Perez-Gil, Amalia ;
Cabriada-Nuno, Valentin ;
Cano-Pumarega, Irene ;
Corral-Penafiel, Jaime ;
Diaz-Cambriles, Trinidad ;
Mediano, Olga ;
Dalmau-Arias, Joan ;
Farre, Ramon ;
Gozal, David .
FRONTIERS IN NEUROLOGY, 2018, 9
[6]  
AMBROSIO G, 1993, J BIOL CHEM, V268, P18532
[7]  
Araki Kazutaka, 2012, Cold Spring Harb Perspect Biol, V4, pa015438, DOI 10.1101/cshperspect.a015438
[8]  
Arvindam US, 2021, J IMMUNOL, V206
[9]   Characteristics of the Tumor Microenvironment That Influence Immune Cell Functions: Hypoxia, Oxidative Stress, Metabolic Alterations [J].
Augustin, Ryan C. ;
Delgoffe, Greg M. ;
Najjar, Yana G. .
CANCERS, 2020, 12 (12) :1-17
[10]   The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression [J].
B'chir, Wafa ;
Maurin, Anne-Catherine ;
Carraro, Valerie ;
Averous, Julien ;
Jousse, Celine ;
Muranishi, Yuki ;
Parry, Laurent ;
Stepien, Georges ;
Fafournoux, Pierre ;
Bruhat, Alain .
NUCLEIC ACIDS RESEARCH, 2013, 41 (16) :7683-7699