PCSK9 and cancer: Rethinking the link.

Autor: Mahboobnia K; Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Pirro M; Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy., Marini E; Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy., Grignani F; Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy., Bezsonov EE; Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Institute of Human Morphology, 3 Tsyurupa Street, Moscow 117418, Russia; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia., Jamialahmadi T; Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Sahebkar A; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: sahebkara@mums.ac.ir.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Aug; Vol. 140, pp. 111758. Date of Electronic Publication: 2021 May 28.
DOI: 10.1016/j.biopha.2021.111758
Abstrakt: Background: Cancer is emerging as a major problem globally, as it accounts for the second cause of death despite medical advances. According to epidemiological and basic studies, cholesterol is involved in cancer progression and there are abnormalities in cholesterol metabolism of cancer cells including prostate, breast, and colorectal carcinomas. However, the importance of cholesterol in carcinogenesis and thereby the role of cholesterol homeostasis as a therapeutic target is still a debated area in cancer therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9), a serine protease, modulates cholesterol metabolism by attachment to the LDL receptor (LDLR) and reducing its recycling by targeting the receptor for lysosomal destruction. Published research has shown that PCSK9 is also involved in degradation of other LDLR family members namely very-low-density-lipoprotein receptor (VLDLR), lipoprotein receptor-related protein 1 (LRP-1), and apolipoprotein E receptor 2 (ApoER2). As a result, this protein represents an interesting therapeutic target for the treatment of hypercholesterolemia. Interestingly, clinical trials on PCSK9-specific monoclonal antibodies have reported promising results with high efficacy in lowering LDL-C and in turn reducing cardiovascular complications. It is important to note that PCSK9 mediates several other pathways apart from its role in lipid homeostasis, including antiviral activity, hepatic regeneration, neuronal apoptosis, and modulation of various signaling pathways. Furthermore, recent literature has illustrated that PCSK9 is closely associated with incidence and progression of several cancers. In a number of studies, PCSK9 siRNA was shown to effectively suppress the proliferation and invasion of the several studied tumor cells. Hence, a novel application of PCSK9 inhibitors/silencers in cancer/metastasis could be considered. However, due to poor data on effectiveness and safety of PCSK9 inhibitors in cancer, the impact of PCSK9 inhibition in these pathological conditions is still unknown.
Search Methods: A vast literature search was conducted to find intended studies from 1956 up to 2020, and inclusion criteria were original peer-reviewed publications.
Purpose of Review: To date, PCSK9 has been scantly investigated in cancer. The question that needs to be discussed is "How does PCSK9 act in cancer pathophysiology and what are the risks or benefits associated to its inhibition?". We reviewed the available publications highlighting the contribution of this proprotein convertase in pathways related to cancer, with focus on the potential implications of its long-term pharmacological inhibition in cancer therapy.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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