Insulin/IGF Axis and the Receptor for Advanced Glycation End Products: Role in Meta-inflammation and Potential in Cancer Therapy.

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2023-07-11 DOI:10.1210/endrev/bnad005
Veronica Vella, Rosamaria Lappano, Eduardo Bonavita, Marcello Maggiolini, Robert Bryan Clarke, Antonino Belfiore, Ernestina Marianna De Francesco
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引用次数: 8

Abstract

In metabolic conditions such as obesity and diabetes, which are associated with deregulated signaling of the insulin/insulin-like growth factor system (IIGFs), inflammation plays a dominant role. In cancer, IIGFs is implicated in disease progression, particularly during obesity and diabetes; however, further mediators may act in concert with IIGFs to trigger meta-inflammation. The receptor for advanced glycation end-products (RAGE) and its ligands bridge together metabolism and inflammation in obesity, diabetes, and cancer. Herein, we summarize the main mechanisms of meta-inflammation in malignancies associated with obesity and diabetes; we provide our readers with the most recent understanding and conceptual advances on the role of RAGE at the crossroad between impaired metabolism and inflammation, toward disease aggressiveness. We inform on the potential hubs of cross-communications driven by aberrant RAGE axis and dysfunctional IIGFs in the tumor microenvironment. Furthermore, we offer a rationalized view on the opportunity to terminate meta-inflammation via targeting RAGE pathway, and on the possibility to shut its molecular connections with IIGFs, toward a better control of diabetes- and obesity-associated cancers.

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胰岛素/IGF轴和晚期糖基化终产物受体:在晚期炎症中的作用和癌症治疗的潜力。
在代谢条件下,如肥胖和糖尿病,这与胰岛素/胰岛素样生长因子系统(IIGFs)信号失调有关,炎症起主导作用。在癌症中,IIGFs与疾病进展有关,特别是在肥胖和糖尿病期间;然而,进一步的介质可能与iigf协同作用,引发元炎症。晚期糖基化终产物受体(RAGE)及其配体在肥胖、糖尿病和癌症的代谢和炎症中起桥梁作用。在此,我们总结了与肥胖和糖尿病相关的恶性肿瘤中meta炎症的主要机制;我们为读者提供RAGE在代谢受损、炎症和疾病侵袭性之间的十字路口的作用的最新理解和概念进展。我们报告了肿瘤微环境中由异常RAGE轴和功能失调iigf驱动的潜在交叉通信枢纽。此外,我们提供了一个合理的观点,即通过靶向RAGE途径终止元炎症的机会,以及关闭其与iigf分子连接的可能性,从而更好地控制糖尿病和肥胖相关癌症。
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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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