Activation of the receptor for glycation end products (RAGE) by its ligands in pancreatic cancer cells

• DOI: 10.1096/fasebj.2019.33.1_supplement.476.11
• Publication Date: 2021-06-22T00:37:56Z
• Authors: Sultan Kadasah; Swetha Thiyagarajan; Stefan Vetter; Estelle Leclerc
• Keywords: RAGE; HMGB1; Ectodomain

Pancreatic cancer is one of the most harmful and lethal cancers in United States. It fourth leading cause death, with only 8.5% patients surviving more than 5 years. The receptor for advanced glycation end products (RAGE) has been associated progression development pancreatic cancer. RAGE ligands, Advanced Glycation End (AGE), proteins S100 family, chromatin binding protein high-mobility group box 1 (HMGB1), have all shown to be present high levels tumors. In addition, HMGB1 secreted by dying cells exposed cytotoxic drugs. Activation its ligands leads activation distinct signaling pathways, resulting translocation transcription factor NF-κB into nucleus. As a result, many genes controlling cell proliferation, adhesion migration are upregulated, enhanced tumor growth. Although trans-membrane protein, it currently not known if needs at surface order activated ligands: indeed, intra- extracellular functions. ectodomain consists three immunoglobulin-like domains (V, C1 C2), V being sites interaction ligands. Previous reports suggest that C2 domain important dimerization, but role well understood. To better understand function, we transfected (Panc-1 MIA PaCa-2) plasmid expressing deleted (RAGE-ΔC2). We observed RAGE-ΔC2 localized endoplasmic reticulum whereas full-length was mostly cell-surface. Based on these observations, hypothesize cell-surface localization key cannot transduce signals from test our hypothesis, will compare (AGEs, S100P S100A8/A9) either or RAGE-ΔC2. use luciferase reporter containing response elements measure changes cells. anticipate lower activities RAGE, upon stimulation discuss outcomes this study. Support Funding Information 1- College Health Professions NDSU 2- NIH Grant Number P20GM109024 National Institute General Medicine (NIGMS). 3- Jazan University Saudi Arabia.4- Arabia Culture Mission (SACM). This abstract Experimental Biology 2019 Meeting. There no full text article published FASEB Journal.