Bordeaux Institute of Oncology (BRIC), INSERM U1312, University of Bordeaux, F-33000 Bordeaux, France.
Laboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute, IRCM, University of Montreal, Montreal, QC H2W 1R7, Canada.
Cells. 2022 Dec 19;11(24):4132. doi: 10.3390/cells11244132.
Metabolic rewiring and defective immune responses are considered to be the main driving forces sustaining cell growth and oncogenesis in many cancers. The atypical enzyme, proprotein convertase subtilisin/kexin type 9 (PCSK9), is produced by the liver in large amounts and plays a major role in lipid metabolism via the control of the low density lipoprotein receptor (LDLR) and other cell surface receptors. In this context, many clinical studies have clearly demonstrated the high efficacy of PCSK9 inhibitors in treating hyperlipidemia and cardiovascular diseases. Recent data implicated PCSK9 in the degradation of major histocompatibility complex I (MHC-I) receptors and the immune system as well as in other physiological activities. This review highlights the complex crosstalk between PCSK9, lipid metabolism and immunosuppression and underlines the latest advances in understanding the involvement of this convertase in other critical functions. We present a comprehensive assessment of the different strategies targeting PCSK9 and show how these approaches could be extended to future therapeutic options to treat cancers with a main focus on the liver.
代谢重编程和免疫功能缺陷被认为是维持许多癌症细胞生长和癌变的主要驱动力。非典型酶原蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）在肝脏中大量产生，通过控制低密度脂蛋白受体（LDLR）和其他细胞表面受体在脂质代谢中发挥主要作用。在这种情况下，许多临床研究清楚地表明，PCSK9 抑制剂在治疗高脂血症和心血管疾病方面非常有效。最近的数据表明，PCSK9 参与主要组织相容性复合体 I（MHC-I）受体和免疫系统的降解以及其他生理活动。本综述强调了 PCSK9、脂质代谢和免疫抑制之间的复杂相互作用，并强调了理解该转化酶在其他关键功能中的最新进展。我们全面评估了针对 PCSK9 的不同策略，并展示了这些方法如何扩展到未来的治疗选择，以治疗以肝脏为主的癌症。
