cancers Review The Unfolded Protein Response in Breast Cancer Eoghan P. McGrath 1,2 , Susan E. Logue 1,2 , Katarzyna Mnich 1,2 , Shane Deegan 1,2, Richard Jäger 3 , Adrienne M. Gorman 1,2 and Afshin Samali 1,2,* 1 Apoptosis Research Centre, National University of Ireland (NUI), Galway, University Road, Galway, H91 TK33 Galway, Ireland;
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[email protected] (A.M.G.) 2 School of Natural Sciences, NUI Galway, University Road, H91 TK33 Galway, Ireland 3 Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, 53359 Rheinbach, Germany;
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[email protected]; Tel.: +353-91-492440 Received: 3 August 2018; Accepted: 18 September 2018; Published: 21 September 2018 Abstract: In 2018, in the US alone, it is estimated that 268,670 people will be diagnosed with breast cancer, and that 41,400 will die from it. Since breast cancers often become resistant to therapies, and certain breast cancers lack therapeutic targets, new approaches are urgently required. A cell-stress response pathway, the unfolded protein response (UPR), has emerged as a promising target for the development of novel breast cancer treatments. This pathway is activated in response to a disturbance in endoplasmic reticulum (ER) homeostasis but has diverse physiological and disease-specific functions. In breast cancer, UPR signalling promotes a malignant phenotype and can confer tumours with resistance to widely used therapies. Here, we review several roles for UPR signalling in breast cancer, highlighting UPR-mediated therapy resistance and the potential for targeting the UPR alone or in combination with existing therapies.