Protein Advanced Glycation End Products and Their Implications in Pancreatic Cancer

Authors

Lakmini Senavirathna
Sheng Pan
Ru Chen

Publication Date

11-1-2023

Journal

Cancer Prevention Research

DOI

10.1158/1940-6207.CAPR-23-0162

PMID

37578815

PMCID

PMC10843555

PubMedCentral® Posted Date

5-1-2024

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Humans, Glycation End Products, Advanced, Receptor for Advanced Glycation End Products, Proteome, Pancreatic Neoplasms, glycation, advanced glycation end products (AGEs), RAGE, pancreatic cancer, proteomics, mass spectrometry

Abstract

Protein advanced glycation end products (AGE) formed by nonenzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for AGEs (RAGE), triggering intricate mechanisms that are etiologically related to various chronic diseases, including pancreatic cancer. Many common risk factors of pancreatic cancer are the major sources for the formation of protein AGEs and glycative stress in the human body. Abnormal accumulation of protein AGEs can impair the cellular proteome and promote AGE-RAGE driven pro-inflammatory signaling cascades, leading to increased oxidative stress, protease resistance, protein dysregulation, transcription activity of STAT, NF-κB, and AP-1, aberrant status in ubiquitin-proteasome system and autophagy, as well as other molecular events that are susceptible for the carcinogenic transformation towards the development of neoplasms. Here, we review studies to highlight our understanding in the orchestrated molecular events in bridging the impaired proteome, dysregulated functional networks, and cancer hallmarks initiated upon protein AGE formation and accumulation in pancreatic cancer.