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AGE-RAGE synergy influences programmed cell death signaling to promote cancer

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Abstract

Advanced glycation end products (AGEs) are formed as a result of non-enzymatic reaction between the free reducing sugars and proteins, lipids, or nucleic acids. AGEs are predominantly synthesized during chronic hyperglycemic conditions or aging. AGEs interact with their receptor RAGE and activate various sets of genes and proteins of the signal transduction pathway. Accumulation of AGEs and upregulated expression of RAGE is associated with various pathological conditions including diabetes, cardiovascular diseases, neurodegenerative disorders, and cancer. The role of AGE-RAGE signaling has been demonstrated in the progression of various types of cancer and other pathological disorders. The expression of RAGE increases manifold during cancer progression. The activation of AGE-RAGE signaling also perturbs the cellular redox balance and modulates various cell death pathways. The programmed cell death signaling often altered during the progression of malignancies. The cellular reprogramming of AGE-RAGE signaling with cell death machinery during tumorigenesis is interesting to understand the complex signaling mechanism of cancer cells. The present review focus on multiple molecular paradigms relevant to cell death particularly Apoptosis, Autophagy, and Necroptosis that are considerably influenced by the AGE-RAGE signaling in the cancer cells. Furthermore, the review also attempts to shed light on the provenience of AGE-RAGE signaling on oxidative stress and consequences of cell survival mechanism of cancer cells.

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Abbreviations

AGE:

Advanced glycation end products

Akt:

Protein kinase B

DAMPs:

Damage-associated molecular patterns

ERK:

Extracellular-signal-regulated kinase

HMGB1:

High‐mobility group box 1

JAK:

Janus kinase

MAPK:

Mitogen-activated protein kinase

NF-kB:

Nuclear factor kappa B

NOX:

NADPH oxidase

Nrf-2:

Nuclear factor erythroid 2-related factor 2

PAMPs:

Pathogen-associated molecular patterns

PI3K:

Phosphoinositide 3-kinases

RAGE:

Receptor of advanced glycation endproducts

ROS:

Reactive oxygen species

STAT-3:

Signal transducer and activator of transcription 3

TLRs:

Toll-like receptors

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Acknowledgements

SERB, Department of Science & Technology, New Delhi, Government of India is acknowledged for providing research Grant (EMR/2016/002574) to Chandramani Pathak. ICMR and DST-INSPIRE are gratefully acknowledged for providing senior research fellowship to Foram U. Vaidya and Bhargav N. Waghela. Indian Institute of Advanced Research, Puri foundation for education in India is gratefully acknowledged for providing research Infrastructure.

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  1. Bhargav N. Waghela and Foram U. Vaidya have an equal contribution.

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  1. Cell Biology Laboratory, School of Biological Sciences & Biotechnology, Indian Institute of Advanced Research, Koba Institutional Area, Gandhinagar, Gujarat, 382426, India

    Bhargav N. Waghela, Foram U. Vaidya, Abu Sufiyan Chhipa, Budhi Sagar Tiwari & Chandramani Pathak

  2. Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT, 06519, USA

    Kishu Ranjan

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Waghela, B.N., Vaidya, F.U., Ranjan, K. et al. AGE-RAGE synergy influences programmed cell death signaling to promote cancer. Mol Cell Biochem 476, 585–598 (2021). https://doi.org/10.1007/s11010-020-03928-y

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