The Glucose-Regulated Protein78 (GRP78) in the Unfolded Protein Response (UPR) Pathway: A Potential Therapeutic Target for Breast Cancer.

Mojgan Noroozi Karimabad, Seyedeh Atekeh Torabizadeh, Maryam Mohammad Sadeghipour

Journal: Anti-cancer agents in medicinal chemistry 2023;23(5):505-524

PMID: 36017846

Abstract

Amongst all types of cancers, breast cancer is recognized as the most common cancer and a principal cause of morbidity and mortality in women. Endoplasmic reticulum (ER) stress pathways are primarily activated in cancer cells and activate a signaling network called the unfolded protein response (UPR). Many tumors, by activating the UPR pathway, allow them to adapt and grow under stressful conditions. UPR is usually inactive in non-tumor cells, while it is active in tumor cells, so it is appropriate to develop new breast cancer therapies. A protein that regulates UPR is 78 KDa Glucose-Regulated Protein (GRP78). Usually, the GRP78 level in the cell is relatively low but increases significantly under stresses that affect the ER and calcium homeostasis, and increases resistance to chemotherapy. GRP78 drug suppressors could provide promising anticancer therapeutics. Therefore, understanding the molecular mechanism of GRP78 in cancer and identifying drugs that target GRP78 is essential for the treatment of breast cancer. In this review, we investigate the role of GRP78 in the pathogenesis of breast cancer.

Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Address: Department of Clinical Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.; Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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