Role and Mechanisms of RAGE-Ligand Complexes and RAGE-Inhibitors in Cancer Progression

• Published in: International journal of molecular sciences 2020-05, Vol.21 (10), p.3613
• Main Authors: El-Far, Ali H, Sroga, Grazyna, Jaouni, Soad K Al, Mousa, Shaker A
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Advanced glycosylation end products; AGEs; AKT protein; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Autophagy; Cancer; Carcinogenesis; Carcinogens; Cell adhesion & migration; Cell cycle; Cell division; Cell growth; Colorectal cancer; Cyclin-dependent kinases; Diabetes mellitus; Dimerization; Glycation End Products, Advanced - antagonists & inhibitors; Glycation End Products, Advanced - metabolism; Glycosylation; Growth factors; HMGB1; HMGB1 protein; HMGB1 Protein - antagonists & inhibitors; HMGB1 Protein - metabolism; Humans; Kinases; Ligands; Liver cancer; Matrix metalloproteinase; Matrix metalloproteinases; Metastasis; MicroRNAs; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; NF-κB protein; Oligomerization; Oral cancer; Oxidation; p53 Protein; Phosphorylation; Prostate; Proteins; RAGE-inhibitors; RAGE-ligands; Rapamycin; Review; S100 Proteins - antagonists & inhibitors; S100 Proteins - metabolism; S100s; Self-association; Signal Transduction; Thyroid cancer; TOR protein; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21103613

Interactions of the receptor for advanced glycation end product (RAGE) and its ligands in the context of their role in diabetes mellitus, inflammation, and carcinogenesis have been extensively investigated. This review focuses on the role of RAGE-ligands and anti-RAGE drugs capable of controlling cancer progression. Different studies have demonstrated interaction of RAGE with a diverse range of acidic (negatively charged) ligands such as advanced glycation end products (AGEs), high-mobility group box1 (HMGB1), and S100s, and their importance to cancer progression. Some RAGE-ligands displayed effects on anti- and pro-apoptotic proteins through upregulation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF- B) pathways, while downregulating p53 in cancer progression. In addition, RAGE may undergo ligand-driven multimodal dimerization or oligomerization mediated through self-association of some of its subunits. We conclude our review by proposing possible future lines of study that could result in control of cancer progression through RAGE inhibition.