Hypoxia driven glycation: Mechanisms and therapeutic opportunities

Semin Cancer Biol. 2018 Apr:49:75-82. doi: 10.1016/j.semcancer.2017.05.008. Epub 2017 May 22.

Abstract

Tumor masses are deprived of oxygen and characterized by enhanced glucose uptake followed by glycolysis. Elevated glucose levels induce non-enzymatic glycosylation or glycation of proteins which leads to accumulation of advanced glycation end products (AGE). These AGE molecules bind to their respective receptors called the receptor for advanced glycation end products (RAGE) and initiate several aberrant signaling pathways leading to onset of diseases such as diabetes, Alzheimer's, atherosclerosis, heart failure and cancer. The role of AGE in cancer progression is being extensively studied in recent years. As cancer cells are hypoxic in nature and adapted to glycolysis, which induces glycation, its effects need to be understood in greater detail. Since AGE-RAGE signaling is involved in cancer progression, inhibition of AGE-RAGE interaction could be a potential therapeutic target. The purpose of this review is to highlight the role of AGE-RAGE interaction in hypoxic cancer cells.

Keywords: Advanced glycation end products; Cancer; Glycation; Hif1α; Hypoxia; RAGE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / metabolism*
  • Glycation End Products, Advanced / antagonists & inhibitors
  • Glycation End Products, Advanced / metabolism
  • Glycosylation* / drug effects
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Molecular Targeted Therapy
  • Protein Binding / drug effects
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Glycation End Products, Advanced
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptor for Advanced Glycation End Products