IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India; Department of Biosciences, Integral University, Lucknow, India.
IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India; Department of Biosciences, Integral University, Lucknow, India.
Semin Cancer Biol. 2018 Apr;49:44-55. doi: 10.1016/j.semcancer.2017.07.001. Epub 2017 Jul 13.
Impaired awareness of glycation biology in cancer initiation and progression is one of the fundamental reasons for its meticulous investigation of the molecules involved in signalling pathway. Glycation of biological macromolecules results in the progression of advanced glycation end-products (AGEs) that proliferates the process of carcinogenesis by activation of transcription factors and release of cytokines. The receptor for advanced glycation end-products (RAGEs) with the binding of its different ligands like; AGEs, HMGB1 and S100 activate the signalling arrays. The activation of downstream signalling pathway ultimately leads to the pathophysiological conditions of diabetes, ageing, neurological disorders and cancers as well as a result of the activation of transcription factors which is discussed in the main body text of this review. However, there might be a likelihood of the positive effect of the HMGB1 and S100 proteins in cancer. Still, some untouched mechanisms might be responsible for the establishment of the function of AGE-RAGE or AGE-sRAGE axis activation that leads to the friend-foe association with the cancers. The levels of RAGE and s-RAGE may be a useful biomarker of ligand-RAGE pathway activation and cancer. Thus, the possibility of providing a potential complement to carcinogenesis is very high which might be an interesting target for therapeutic interventions. This article is an insightful assessment on AGE, RAGE and s-RAGE for its possible role in cancer onset and progression. The novel therapeutic targets for cancer prevention or inhibition are also explained in brief in relation to AGE and RAGE.
在癌症的发生和发展过程中,对糖化生物学认识不足是其对参与信号通路的分子进行细致研究的根本原因之一。生物大分子的糖化导致晚期糖基化终产物(AGEs)的进展,通过转录因子的激活和细胞因子的释放,促进了致癌过程。晚期糖基化终产物受体(RAGE)与其不同配体(如 AGEs、HMGB1 和 S100)结合,激活信号阵列。下游信号通路的激活最终导致糖尿病、衰老、神经紊乱和癌症的病理生理状况,以及转录因子的激活,这在本文的正文部分进行了讨论。然而,HMGB1 和 S100 蛋白在癌症中可能具有积极作用。尽管如此,一些未被触及的机制可能负责建立 AGE-RAGE 或 AGE-sRAGE 轴激活的功能,导致与癌症的友敌关系。RAGE 和 s-RAGE 的水平可能是配体-RAGE 通路激活和癌症的有用生物标志物。因此,为致癌作用提供潜在补充的可能性非常高,这可能是治疗干预的一个有趣目标。本文对 AGE、RAGE 和 s-RAGE 在癌症发生和发展中的可能作用进行了深入评估。还简要解释了与 AGE 和 RAGE 相关的癌症预防或抑制的新治疗靶点。