scholarly journals Expression and splicing of the unfolded protein response gene XBP-1 are significantly associated with clinical outcome of endocrine-treated breast cancer

2008 ◽  
Vol 123 (1) ◽  
pp. 85-88 ◽  
Author(s):  
Michael P.A. Davies ◽  
Dong Liu Barraclough ◽  
Ceri Stewart ◽  
Kathryn A. Joyce ◽  
Richard M. Eccles ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Unfolded Protein Response ◽  
Response Gene ◽  
Unfolded Protein ◽  
Treated Breast ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Treated Breast Cancer

scholarly journals Rapid Induction of the Unfolded Protein Response and Apoptosis by Estrogen Mimic TTC-352 for the Treatment of Endocrine-Resistant Breast Cancer

2020 ◽  
Vol 20 (1) ◽  
pp. 11-25
Author(s):  
Balkees Abderrahman ◽  
Philipp Y. Maximov ◽  
Ramona F. Curpan ◽  
Sean W. Fanning ◽  
Jay S. Hanspal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Rapid Induction ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals KDM4B-regulated unfolded protein response as a therapeutic vulnerability in PTEN-deficient breast cancer

2018 ◽  
Vol 215 (11) ◽  
pp. 2833-2849 ◽  
Author(s):  
Wenyu Wang ◽  
Gokce Oguz ◽  
Puay Leng Lee ◽  
Yi Bao ◽  
Panpan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Unfolded Protein Response ◽  
Breast Cancers ◽  
Akt Inhibitor ◽  
Unfolded Protein ◽  
Crucial Component ◽  
Pi3k Inhibition ◽  
Demethylase Activity ◽  
The Unfolded Protein Response ◽  
Protein Response

PTEN deficiency in breast cancer leads to resistance to PI3K–AKT inhibitor treatment despite aberrant activation of this signaling pathway. Here, we report that genetic depletion or small molecule inhibition of KDM4B histone demethylase activates the unfolded protein response (UPR) pathway and results in preferential apoptosis in PTEN-deficient triple-negative breast cancers (TNBCs). Intriguingly, this function of KDM4B on UPR requires its demethylase activity but is independent of its canonical role in histone modification, and acts through its cytoplasmic interaction with eIF2α, a crucial component of UPR signaling, resulting in reduced phosphorylation of this component. Targeting KDM4B in combination with PI3K inhibition induces further activation of UPR, leading to robust synergy in apoptosis. These findings identify KDM4B as a therapeutic vulnerability in PTEN-deficient TNBC that otherwise would be resistant to PI3K inhibition.

scholarly journals Endoplasmic Reticulum Stress and Unfolded Protein Response in Breast Cancer: The Balance between Apoptosis and Autophagy and Its Role in Drug Resistance

2019 ◽  
Vol 20 (4) ◽  
pp. 857 ◽  
Author(s):  
Lorenza Sisinni ◽  
Michele Pietrafesa ◽  
Silvia Lepore ◽  
Francesca Maddalena ◽  
Valentina Condelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Inflammatory Diseases ◽  
Unfolded Protein ◽  
Chronic Activation ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
The Relationship

The unfolded protein response (UPR) is a stress response activated by the accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) and its uncontrolled activation is mechanistically responsible for several human pathologies, including metabolic, neurodegenerative, and inflammatory diseases, and cancer. Indeed, ER stress and the downstream UPR activation lead to changes in the levels and activities of key regulators of cell survival and autophagy and this is physiologically finalized to restore metabolic homeostasis with the integration of pro-death or/and pro-survival signals. By contrast, the chronic activation of UPR in cancer cells is widely considered a mechanism of tumor progression. In this review, we focus on the relationship between ER stress, apoptosis, and autophagy in human breast cancer and the interplay between the activation of UPR and resistance to anticancer therapies with the aim to disclose novel therapeutic scenarios. The hypothesis that autophagy and UPR may provide novel molecular targets in human malignancies is discussed.

scholarly journals Activation and clinical significance of the unfolded protein response in breast cancer

2009 ◽  
Vol 101 (10) ◽  
pp. 1692-1698 ◽  
Author(s):  
P Scriven ◽  
S Coulson ◽  
R Haines ◽  
S Balasubramanian ◽  
S Cross ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Unfolded Protein Response ◽  
Clinical Significance ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Endoplasmic reticulum stress, the unfolded protein response, and gene network modeling in antiestrogen resistant breast cancer

2011 ◽  
Vol 5 (1) ◽  
Author(s):  
Robert Clarke ◽  
Ayesha N. Shajahan ◽  
Yue Wang ◽  
John J. Tyson ◽  
Rebecca B. Riggins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Unfolded Protein Response ◽  
Network Modeling ◽  
Endocrine Resistance ◽  
Molecular Signaling ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractLack of understanding of endocrine resistance remains one of the major challenges for breast cancer researchers, clinicians, and patients. Current reductionist approaches to understanding the molecular signaling driving resistance have offered mostly incremental progress over the past 10 years. As the field of systems biology has begun to mature, the approaches and network modeling tools being developed and applied therein offer a different way to think about how molecular signaling and the regulation of crucial cellular functions are integrated. To gain novel insights, we first describe some of the key challenges facing network modeling of endocrine resistance, many of which arise from the properties of the data spaces being studied. We then use activation of the unfolded protein response (UPR) following induction of endoplasmic reticulum stress in breast cancer cells by antiestrogens, to illustrate our approaches to computational modeling. Activation of UPR is a key determinant of cell fate decision-making and regulation of autophagy and apoptosis. These initial studies provide insight into a small subnetwork topology obtained using differential dependency network analysis and focused on the UPR gene XBP1. The XBP1 subnetwork topology incorporates BCAR3, BCL2, BIK, NF-κB, and other genes as nodes; the connecting edges represent the dependency structures among these nodes. As data from ongoing cellular and molecular studies become available, we will build detailed mathematical models of this XBP1-UPR network.

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