Eva Taslima Akter, Barua Nizum, Chowdhury Md Mustafiz, Yeasmin Sharfin, Rakib Ahmed, Islam Mohammad Rashedul, Emran Talha Bin, Simal-Gandara Jesus
Department of Pharmacy, Faculty of Biological Science, University of Chittagong, Chittagong, Bangladesh.
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh.
Crit Rev Food Sci Nutr. 2022;62(10):2655-2672. doi: 10.1080/10408398.2020.1856771. Epub 2020 Dec 12.
Receptor for advanced glycation end-products (RAGE) is a multifunctional receptor binds a broad spectrum of ligands and mediates responses to cell damage and stress conditions. It also activates programs leading to acute and chronic inflammation and implicated in several pathological diseases, including cancer. In this review, we presented the non-enzymatic reaction of reducing sugar with the amino groups of proteins, lipids, and nucleic acids. This reaction initiates a complex series of rearrangements and dehydrations, and then produces a class of irreversibly cross-linked heterogeneous fluorescent moieties, termed advanced glycation end products (AGEs). There is a growing body of evidence that interaction of processes food-related AGEs with a cell surface receptor RAGE brings out the generation of oxidative stress and subsequently evokes proliferative, angiogenic and inflammatory reactions, thereby being involved in the development and progression of various types of cancers. This review is an insightful assessment of molecular mechanisms through which RAGE signaling contributes to the enhancement and survival of the tumorigenic cell. Here we summarize the procurement of individual ligands of RAGE like amphoterin, calcium-binding proteins, and resultant mediation of RAGE signaling pathway, which partially can elucidate the elevated risk of several cancers. Besides, we summarize many factors or conditions including APE1 (apurinic/apyrimidinic endonuclease 1), retinol mutations, retinoblastoma (Rb), proteinase 3 (PR3) hypoxia and so on through which RAGE signaling presents an establishment of cancerous environment. Additionally, we also reviewed some recent findings that give shreds of evidence for presenting the role of RAGE and its ligands in the advanced stage of cancers.
晚期糖基化终末产物受体（RAGE）是一种多功能受体，可结合多种配体，并介导细胞对损伤和应激条件的反应。它还能激活导致急性和慢性炎症的程序，并与包括癌症在内的多种病理疾病有关。在本综述中，我们介绍了还原糖与蛋白质、脂质和核酸的氨基发生的非酶促反应。该反应引发一系列复杂的重排和脱水反应，然后产生一类不可逆交联的异质荧光基团，称为晚期糖基化终末产物（AGEs）。越来越多的证据表明，与食品相关的AGEs与细胞表面受体RAGE相互作用会产生氧化应激，随后引发增殖、血管生成和炎症反应，从而参与各种类型癌症的发生和发展。本综述对RAGE信号传导促进致瘤细胞增殖和存活的分子机制进行了有见地的评估。在这里，我们总结了RAGE的个别配体如双调蛋白、钙结合蛋白的获得以及由此产生的RAGE信号通路的介导作用，这部分可以解释几种癌症风险的升高。此外，我们总结了许多因素或条件，包括脱嘌呤/脱嘧啶内切酶1（APE1）、视黄醇突变、视网膜母细胞瘤（Rb）、蛋白酶3（PR3）、缺氧等，通过这些因素或条件RAGE信号传导呈现出癌环境的建立。此外，我们还回顾了一些最新发现，这些发现为RAGE及其配体在癌症晚期的作用提供了证据。
