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Impact of Advanced Glycation End products (AGEs) and its receptor (RAGE) on cancer metabolic signaling pathways and its progression

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Abstract

Cancer is a complex disease with a 5–10% hereditary base, but nutrition, lifestyle, and the environment we are exposed to influence 90–95% of cancers. Due to rapid westernization, the diet we consume is rich in advanced glycation end products (AGEs). AGEs are the heterogeneous group of compounds formed by non-enzymatic reactions between reducing sugars and amino groups of proteins, lipids, and nucleic acids. Its implication is confirmed in many chronic conditions such as diabetes, renal, cardiovascular diseases, and aging however its role in cancer development has been understudied. Cancer cells are continuously exposed to AGEs due to their increased production, owing to its high metabolic rate and aerobic glycolysis. AGEs accumulation led to glycative stress which in turn stimulates oxidative stress and inflammation, through its receptor known as receptor for advanced glycation end products (RAGE). RAGE mediates crosstalk between the tumour cells and its microenvironment components to induce hypoxia, mitochondrial dysfunction, endoplasmic reticulum stress, autophagy, epigenetic modification, and cancer stemness. This emphasizes AGEs as an essential driving factor in different aspects of cancer development, but the exact molecular mechanism has to be explored. Thus, this review gives an insight into the pathological role of AGEs at the bio-molecular level in the tumourigenesis and progression of cancer in terms of the tumour microenvironment, invasion, and metastasis. Further, the compiled clinical data relating to the AGE-RAGE axis associated with different cancers and its potential inhibitors have been discussed.

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Abbreviations

ADAM 10:

A disintegrin and metalloproteinase10

AGEs:

Advanced glycation end products

ALES:

Advanced lipoxidation end products

AP-1:

Activator protein 1

ATF6:

Activating transcription factor 6

Bcl-2:

B-cell lymphoma-2

Bcl-xL:

B-cell lymphoma-extra-large

CEL:

Carboxyethyllysine

ChREBP:

Carbohydrate responsive element binding protein

CML:

Carboxymethyllysine

cRAGE:

Cleaved RAGE

ECM:

Extracellular matrix

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated protein kinases

esRAGE:

:Endogenous secretory RAGE

FAK:

Focal adhesion kinase

GLO-I:

Glyoxalase-I

GLUT1:

Glucose transporters 1

GSK-3β :

Glycogen synthase kinase 3 beta

HIF-1α:

Hypoxia inducible factor-1

HMGB1:

High mobility group box 1 protein

HRE:

Hypoxia-response elements

ICAM-1:

 Intercellular cell adhesion molecule 1

IL-1/6:

Interleukin 1/6

IRE1α:

Inositol-requiring enzyme 1α

JAK/ STAT:

Janus kinase/signal transducers and activators of transcription

JNK:

C-Jun N-terminal kinases

MAMs:

Mitochondrial associated molecular membrane

MAPK:

Mitogen-activated protein kinases

MG:

Methylglyoxal

MMP:

Matrix metalloproteinases

MSR-1:

Macrophage scavenger receptor-1

mTOR:

Mammalian target of rapamycin

NF-κB:

Nuclear factor kappa B

NOX:

NADPH oxidase

Nrf-2:

Nuclear factor erythroid 2–related factor 2

PARP:

Poly-ADP-ribose polymerase

PDGF:

Platelet-derived growth factor

PERK:

Pancreatic ER kinase-like ER kinase

RAGE:

Receptor for AGEs

ROS:

Reactive oxygen species

sRAGE:

Soluble RAGE

TGF-β :

Transforming growth factor-β

TNF-α:

Tumour necrosis factor- α

VCAM-1:

Vascular cell adhesion molecule

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The authors acknowledge the Indian Council for Medical Research (ICMR), New Delhi, for providing Senior Research Fellowship to Yadav Sangeeta Muthyalaiah

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  1. Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India

    Yadav Sangeeta Muthyalaiah, Bhavana Jonnalagadda, Cordelia Mano John & Sumathy Arockiasamy

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Correspondence to Sumathy Arockiasamy.

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Muthyalaiah, Y.S., Jonnalagadda, B., John, C.M. et al. Impact of Advanced Glycation End products (AGEs) and its receptor (RAGE) on cancer metabolic signaling pathways and its progression. Glycoconj J 38, 717–734 (2021). https://doi.org/10.1007/s10719-021-10031-x

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