scholarly journals Unfolding anti-tumor immunity: ER stress responses sculpt tolerogenic myeloid cells in cancer

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Juan R. Cubillos-Ruiz ◽  
Eslam Mohamed ◽  
Paulo C. Rodriguez
Keyword(s):  
Er Stress ◽  
Tumor Immunity ◽  
Stress Responses ◽  
Myeloid Cells

scholarly journals Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

2021 ◽  
Author(s):  
Sinan Xiong ◽  
Wee-Joo Chng ◽  
Jianbiao Zhou
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Fate ◽  
Stress Responses ◽  
Plasma Cells ◽  
Reactive Oxygen Species Generation ◽  
Future Research ◽  
And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

scholarly journals Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2α/ATF4/CHOP axis in hepatocellular carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Sanghwa Kim ◽  
Minji Lee ◽  
Yeonhwa Song ◽  
Su-Yeon Lee ◽  
Inhee Choi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Er Stress ◽  
Stress Responses ◽  
Arginine Metabolism ◽  
Tumor Spheroids ◽  
Clinical Value ◽  
Suppressor Activity ◽  
Argininosuccinate Synthase ◽  
Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids. Methods Our comparative proteomic analysis of HCC cells grown in culture as monolayers (2D) and spheroids (3D) revealed that argininosuccinate synthase 1 (ASS1) expression was higher in 3D cells than in 2D cells due to upregulated endoplasmic reticulum (ER) stress responses. We investigated the clinical value of ASS1 in Korean patients with HCC. The mechanism underlying ASS1-mediated tumor suppression was investigated in HCC spheroids. ASS1-mediated improvement of chemotherapy efficiency was observed using high content screening in an HCC xenograft mouse model. Results Studies of tumor tissue from Korean HCC patients showed that, although ASS1 expression was low in most samples, high levels of ASS1 were associated with favorable overall survival of patients. Here, we found that bidirectional interactions between ASS1 ER stress responses in HCC-derived multicellular tumor spheroids can limit HCC progression. ASS1 overexpression effectively inhibited tumor growth and enhanced the efficacy of in vitro and in vivo anti-HCC combination chemotherapy via activation of the PERK/eIF2α/ATF4/CHOP axis, but was not dependent on the status of p53 and arginine metabolism. Conclusions These results demonstrate the critical functional roles for the arginine metabolism–independent tumor suppressor activity of ASS1 in HCC and suggest that upregulating ASS1 in these tumors is a potential strategy in HCC cells with low ASS1 expression.

Acute high-intensity aerobic exercise increases gene expression of calcium-related proteins and activates endoplasmic reticulum stress responses in diabetic hearts

2020 ◽  
pp. 1-14
Author(s):  
H.O. Ness ◽  
K. Ljones ◽  
M. Pinho ◽  
M.A. Høydal
Keyword(s):  
Gene Expression ◽  
Exercise Training ◽  
Er Stress ◽  
Aerobic Exercise ◽  
Stress Responses ◽  
Mitochondrial Respiration ◽  
High Intensity ◽  
Acute Exercise ◽  
Contractile Function ◽  
Aerobic Exercise Training

Regular aerobic exercise training has a wide range of beneficial cardiac effects, but recent data also show that acute very strenuous aerobic exercise may impose a transient cardiac exhaustion. The aim of this study was to assess the response to acute high-intensity aerobic exercise on properties of mitochondrial respiration, cardiomyocyte contractile function, Ca2+ handling and transcriptional changes for key proteins facilitating Ca2+ handling and endoplasmic reticulum (ER) stress responses in type 2 diabetic mice. Diabetic mice were assigned to either sedentary control or an acute bout of exercise, consisting of a 10×4 minutes high-intensity interval treadmill run. Mitochondrial respiration, contractile and Ca2+ handling properties of cardiomyocytes were analysed 1 hour after completion of exercise. Gene expression levels of key Ca2+ handling and ER stress response proteins were measured in cardiac tissue samples harvested 1 hour and 24 hours after exercise. We found no significant changes in mitochondrial respiration, cardiomyocyte contractile function or Ca2+ handling 1 hour after the acute exercise. However, gene expression of Atp2a2, Slc8a1 and Ryr2, encoding proteins involved in cardiomyocyte Ca2+ handling, were all significantly upregulated 24 hours after the acute exercise bout. Acute exercise also altered gene expression of several key proteins in ER stress response and unfolded protein response, including Grp94, total Xbp1, Gadd34, and Atf6. The present results show that despite no significant alterations in functional properties of cardiomyocyte function, Ca2+ handling or mitochondrial respiration following one bout of high intensity aerobic exercise training, the expression of genes involved in Ca2+ handling and key components in ER stress and the unfolded protein response were changed. These transcriptional changes may constitute important steps in initiating adaptive remodelling to exercise training in type 2 diabetes.

scholarly journals Priming anti-tumor immunity by radiotherapy: Dying tumor cell-derived DAMPs trigger endothelial cell activation and recruitment of myeloid cells

2018 ◽  
Vol 8 (1) ◽  
pp. e1523097 ◽  
Author(s):  
Julia Krombach ◽  
Roman Hennel ◽  
Nikko Brix ◽  
Michael Orth ◽  
Ulrike Schoetz ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Tumor Cell ◽  
Tumor Immunity ◽  
Cell Activation ◽  
Myeloid Cells ◽  
Endothelial Cell Activation

Gadd45 modulation of intrinsic and extrinsic stress responses in myeloid cells

2009 ◽  
Vol 218 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Barbara Hoffman ◽  
Dan A. Liebermann
Keyword(s):  
Stress Responses ◽  
Myeloid Cells

scholarly journals Blocking NHE1 stimulates glioma tumor immunity by restoring OXPHOS function of myeloid cells

Theranostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 1295-1309
Author(s):  
Md Nabiul Hasan ◽  
Lanxin Luo ◽  
Dawei Ding ◽  
Shanshan Song ◽  
Mohammad Iqbal H. Bhuiyan ◽  
...  
Keyword(s):  
Tumor Immunity ◽  
Myeloid Cells ◽  
Glioma Tumor

scholarly journals Involvement of Noxa in mediating cellular ER stress responses to lytic virus infection

Virology ◽  
2011 ◽  
Vol 417 (2) ◽  
pp. 293-303 ◽  
Author(s):  
Shaun Rosebeck ◽  
Kuladeep Sudini ◽  
Tiannan Chen ◽  
Douglas W. Leaman
Keyword(s):  
Virus Infection ◽  
Er Stress ◽  
Stress Responses

Vitexin protects isoproterenol induced post myocardial injury by modulating hipposignaling and ER stress responses

2018 ◽  
Vol 496 (2) ◽  
pp. 731-737 ◽  
Author(s):  
Rathinavel Ashokkumar ◽  
Sankar Jamuna ◽  
M.S. Sakeena Sadullah ◽  
S. Niranjali Devaraj
Keyword(s):  
Er Stress ◽  
Stress Responses ◽  
Myocardial Injury

IRE1α–XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain

Science ◽  
2019 ◽  
Vol 365 (6450) ◽  
pp. eaau6499 ◽  
Author(s):  
Sahil Chopra ◽  
Paolo Giovanelli ◽  
Perla Abigail Alvarado-Vazquez ◽  
Sara Alonso ◽  
Minkyung Song ◽  
...  
Keyword(s):  
Er Stress ◽  
Myeloid Cells ◽  
Prostaglandin E ◽  
Prostaglandin E Synthase ◽  
Prostaglandin Biosynthesis ◽  
Stress Sensors ◽  
Prostaglandin Endoperoxide Synthase ◽  
Cox 2 ◽  
Control Pain ◽  
Er Homeostasis

Inositol-requiring enzyme 1[α] (IRE1[α])–X-box binding protein spliced (XBP1) signaling maintains endoplasmic reticulum (ER) homeostasis while controlling immunometabolic processes. Yet, the physiological consequences of IRE1α–XBP1 activation in leukocytes remain unexplored. We found that induction of prostaglandin-endoperoxide synthase 2 (Ptgs2/Cox-2) and prostaglandin E synthase (Ptges/mPGES-1) was compromised in IRE1α-deficient myeloid cells undergoing ER stress or stimulated through pattern recognition receptors. Inducible biosynthesis of prostaglandins, including the pro-algesic mediator prostaglandin E2 (PGE2), was decreased in myeloid cells that lack IRE1α or XBP1 but not other ER stress sensors. Functional XBP1 transactivated the human PTGS2 and PTGES genes to enable optimal PGE2 production. Mice that lack IRE1α–XBP1 in leukocytes, or that were treated with IRE1α inhibitors, demonstrated reduced pain behaviors in PGE2-dependent models of pain. Thus, IRE1α–XBP1 is a mediator of prostaglandin biosynthesis and a potential target to control pain.

scholarly journals Regulation of autophagy by canonical and non-canonical ER stress responses

2020 ◽  
Vol 66 ◽  
pp. 116-128 ◽  
Author(s):  
Monika Bhardwaj ◽  
Nektaria Maria Leli ◽  
Constantinos Koumenis ◽  
Ravi K. Amaravadi
Keyword(s):  
Er Stress ◽  
Stress Responses
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