scholarly journals Activation and Cross-talk between Akt, NF-κB, and Unfolded Protein Response Signaling in 1-LN Prostate Cancer Cells Consequent to Ligation of Cell Surface-associated GRP78

2006 ◽  
Vol 281 (19) ◽  
pp. 13694-13707 ◽  
Author(s):  
Uma Kant Misra ◽  
Rohit Deedwania ◽  
Salvatore Vincent Pizzo
Keyword(s):  
Prostate Cancer ◽  
Cell Surface ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Cross Talk ◽  
Prostate Cancer Cells ◽  
Unfolded Protein ◽  
Protein Response

scholarly journals Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesca Amoroso ◽  
Kimberley Glass ◽  
Reema Singh ◽  
Francisco Liberal ◽  
Rebecca E. Steele ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Radiation Response ◽  
Prostate Cancer Cells ◽  
Short Term Treatment ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractProstate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activation of the UPR using radiation and ONC201, an UPR activator. Treating PCa cells with ONC201 quickly increased the expression of all the key regulators of the UPR and reduced the oxidative phosphorylation, with cell death occurring 72 h later. We exploited this time lag to sensitize prostate cancer cells to radiation through short-term treatment with ONC201. To understand how priming occurred, we performed RNA-Seq analysis and found that ONC201 suppressed the expression of cell cycle and DNA repair factors. In conclusion, we have shown that ONC201 can prime enhanced radiation response.

scholarly journals Metformin Dysregulates the Unfolded Protein Response and the WNT/β-Catenin Pathway in Endometrial Cancer Cells through an AMPK-Independent Mechanism

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1067
Author(s):  
Domenico Conza ◽  
Paola Mirra ◽  
Gaetano Calì ◽  
Luigi Insabato ◽  
Francesca Fiory ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Independent Manner ◽  
Growth And Survival ◽  
Unfolded Protein ◽  
Compound C ◽  
Survival Pathways ◽  
The Unfolded Protein Response ◽  
Protein Response

Multiple lines of evidence suggest that metformin, an antidiabetic drug, exerts anti-tumorigenic effects in different types of cancer. Metformin has been reported to affect cancer cells’ metabolism and proliferation mainly through the activation of AMP-activated protein kinase (AMPK). Here, we show that metformin inhibits, indeed, endometrial cancer cells’ growth and induces apoptosis. More importantly, we report that metformin affects two important pro-survival pathways, such as the Unfolded Protein Response (UPR), following endoplasmic reticulum stress, and the WNT/β-catenin pathway. GRP78, a key protein in the pro-survival arm of the UPR, was indeed downregulated, while GADD153/CHOP, a transcription factor that mediates the pro-apoptotic response of the UPR, was upregulated at both the mRNA and protein level. Furthermore, metformin dramatically inhibited β-catenin mRNA and protein expression. This was paralleled by a reduction in β-catenin transcriptional activity, since metformin inhibited the activity of a TCF/LEF-luciferase promoter. Intriguingly, compound C, a well-known inhibitor of AMPK, was unable to prevent all these effects, suggesting that metformin might inhibit endometrial cancer cells’ growth and survival through the modulation of specific branches of the UPR and the inhibition of the Wnt/β-catenin pathway in an AMPK-independent manner. Our findings may provide new insights on the mechanisms of action of metformin and refine the use of this drug in the treatment of endometrial cancer.

TXNIP links anticipatory unfolded protein response to estrogen reprogramming glucose metabolism in breast cancer cells

Endocrinology ◽  
2021 ◽  
Author(s):  
Yuanzhong Wang ◽  
Shiuan Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Warburg Effect ◽  
Breast Cancer Cells ◽  
Unfolded Protein ◽  
Protein Response

Abstract Estrogen and estrogen receptor (ER) play a fundamental role in breast cancer. To adapt the rapid proliferation of ER+ breast cancer cells, estrogen increases glucose uptake and reprograms glucose metabolism. Meanwhile, estrogen/ER activates the anticipatory unfolded protein response (UPR) preparing cancer cells for the increased protein production required for subsequent cell proliferation. Here, we report that thioredoxin-interacting protein (TXNIP) is an important regulator of glucose metabolism in ER+ breast cancer cells, and estrogen/ER increases glucose uptake and reprograms glucose metabolism via activating anticipatory unfolded protein response (UPR) and subsequently repressing TXNIP expression. By using two widely used ER+ breast cancer cell lines MCF7 and T47D, we showed that MCF7 cells express high TXNIP levels and exhibit mitochondrial oxidative phosphorylation (OXPHOS) phenotype, while T47D cells express low TXNIP levels and display aerobic glycolysis (Warburg effect) phenotype. Knockdown of TXNIP promoted glucose uptake and Warburg effect, while forced overexpression of TXNIP inhibited glucose uptake and Warburg effect. We further showed that estrogen represses TXNIP expression and activates UPR sensor inositol-requiring enzyme 1 (IRE1) via ER in the breast cancer cells, and IRE1 activity is required for estrogen suppression of TXNIP expression and estrogen-induced cell proliferation. Together, our study suggests that TXNIP is involved in estrogen-induced glucose uptake and metabolic reprogramming in ER+ breast cancer cells, and links anticipatory UPR to estrogen reprogramming glucose metabolism.

Sequencing of Argonaute-bound miRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a

2021 ◽  
Author(s):  
Christopher J Fields ◽  
Lu Li ◽  
Nicholas M Hiers ◽  
Tianqi Li ◽  
Peike Sheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Rna Polymerase Ii ◽  
Mirna Biogenesis ◽  
Unfolded Protein ◽  
Colorectal Cancer Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

MicroRNAs (miRNA) are short non-coding RNAs widely implicated in gene regulation. Most metazoan miRNAs utilize the RNase III enzymes Drosha and Dicer for biogenesis. One notable exception is the RNA polymerase II transcription start sites (TSS) miRNAs whose biogenesis does not require Drosha. The functional importance of the TSS-miRNA biogenesis is uncertain. To better understand the function of TSS-miRNAs, we applied a modified Crosslinking, Ligation, and Sequencing of Hybrids on Argonaute (AGO-qCLASH) to identify the targets for TSS-miRNAs in HCT116 colorectal cancer cells with or without DROSHA knockout. We observed that miR-320a hybrids dominate in TSS-miRNA hybrids identified by AGO-qCLASH. Targets for miR-320a are enriched in the eIF2 signaling pathway, a downstream component of the unfolded protein response. Consistently, in miR-320a mimic- and antagomir- transfected cells, differentially expressed genes are enriched in eIF2 signaling. Within the AGO-qCLASH data, we identified the endoplasmic reticulum (ER) chaperone Calnexin as a direct miR-320a target, thus connecting miR-320a to the unfolded protein response. During ER stress, but not amino acid deprivation, miR-320a up-regulates ATF4, a critical transcription factor for resolving ER stress. Our study investigates the targetome of the TSS-miRNAs in colorectal cancer cells and establishes miR-320a as a regulator of unfolded protein response.

scholarly journals Prostate cancer and the unfolded protein response

Oncotarget ◽  
2016 ◽  
Vol 7 (33) ◽  
pp. 54051-54066 ◽  
Author(s):  
Margrethe Storm ◽  
Xia Sheng ◽  
Yke Jildouw Arnoldussen ◽  
Fahri Saatcioglu
Keyword(s):  
Prostate Cancer ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Small Molecule-Induced Mitochondrial Disruption Directs Prostate Cancer Inhibition via Unfolded Protein Response Signaling

Oncotarget ◽  
2013 ◽  
Vol 4 (8) ◽  
pp. 1212-1229 ◽  
Author(s):  
Elizabeth Rico-Bautista ◽  
Wenhong Zhu ◽  
Shinichi Kitada ◽  
Suthakar Ganapathy ◽  
Eric Lau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Unfolded Protein Response ◽  
Small Molecule ◽  
Unfolded Protein ◽  
Mitochondrial Disruption ◽  
Protein Response ◽  
Cancer Inhibition

scholarly journals A Peptidic Unconjugated GRP78/BiP Ligand Modulates the Unfolded Protein Response and Induces Prostate Cancer Cell Death

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e45690 ◽  
Author(s):  
Danilo Maddalo ◽  
Antje Neeb ◽  
Katja Jehle ◽  
Katja Schmitz ◽  
Claudia Muhle-Goll ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Unfolded Protein Response ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Unfolded Protein ◽  
Cancer Cell Death ◽  
The Unfolded Protein Response ◽  
Protein Response
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