Analysis of RAGE Proteome and Interactome in Lung Adenocarcinoma Using PANTHER and STRING Databases

Abstract

Adenocarcinoma accounts for about 40% of all lung cancers. Histological studies indicate a loss of expression of the Receptor for Advanced Glycation End-products (RAGE) in lung adenocarcinoma cells compared to neighboring non-malignant tissue. Gene silencing of RAGE in human lung adenocarcinoma cells was performed and then cells were subjected to LC-MS/MS (n = 3, FDR < 1%). Differentially expressed proteins were analyzed using the PANTHER Classification System and STRING Interactome, identifying functions and protein-protein interaction networks. We observed expression of dominant-negative (DN−) RAGE, an isoform lacking the critical intracellular signaling tail observed in the full length (FL−) RAGE. Proteomic analysis suggests DN-RAGE likely plays a crucial role in cell polarity, metastases, and in cell-cell or cell-matrix complexes through focal adhesion or adherens junction formation. DN-RAGE may also regulate the expression of FL-RAGE and may provide a “switch” that could transition from a pro-inflammatory to a migratory cell as vimentin expression increased along with a reduction in cell polarity proteins. STRING interactome analysis identified seven protein–protein interaction networks involved in the regulation of gene expression, cell organization, cytoskeletal changes, sub-membrane plaque formation, as well as cytokinesis, cell shape, and motility. Suggesting expression of DN-RAGE may contribute to metastases and the development of advanced cancer.