RAGE (Receptor for Advanced Glycation Endproducts), RAGE ligands, and their role in cancer and inflammation

J Transl Med. 2009 Mar 17;7:17. doi: 10.1186/1479-5876-7-17.

Abstract

The Receptor for Advanced Glycation Endproducts [RAGE] is an evolutionarily recent member of the immunoglobulin super-family, encoded in the Class III region of the major histocompatability complex. RAGE is highly expressed only in the lung at readily measurable levels but increases quickly at sites of inflammation, largely on inflammatory and epithelial cells. It is found either as a membrane-bound or soluble protein that is markedly upregulated by stress in epithelial cells, thereby regulating their metabolism and enhancing their central barrier functionality. Activation and upregulation of RAGE by its ligands leads to enhanced survival. Perpetual signaling through RAGE-induced survival pathways in the setting of limited nutrients or oxygenation results in enhanced autophagy, diminished apoptosis, and (with ATP depletion) necrosis. This results in chronic inflammation and in many instances is the setting in which epithelial malignancies arise. RAGE and its isoforms sit in a pivotal role, regulating metabolism, inflammation, and epithelial survival in the setting of stress. Understanding the molecular structure and function of it and its ligands in the setting of inflammation is critically important in understanding the role of this receptor in tumor biology.

Publication types

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

MeSH terms

  • Animals
  • High Mobility Group Proteins / metabolism
  • Humans
  • Inflammation / metabolism*
  • Ligands
  • Neoplasms / metabolism*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism*
  • S100 Proteins / metabolism

Substances

  • High Mobility Group Proteins
  • Ligands
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • S100 Proteins