Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma

Purpose To explore the expression of receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB1) and their role in clear cell renal cell carcinoma (CCRCC) development and progression. Methods Expression of RAGE and HMGB1 was examined in RCC using tissue microarrays. In vitro, quiescent or RAGE-reduced RCC cells were subjected to treatment with HMGB1 and harvested for detecting ERK1/2 phosphorylation via Western blot. Further cell proliferation, migration and invasion were evaluated by Ki-67 immunostaining, wound healing and matrigel invasion assay, respectively. Results (1)Elevated co-expression of RAGE and HMGB1 in CCRCC was correlated positively with patients' clinical parameters including tumor size, nuclear Fuhrman grade and clinical stage. (2)HMGB1 incubation induced ERK1/2 activation in a time-and dose-dependent manner, which could be completely blocked by U0126 (MEK1/2 inhibitor) and partially reversed by RAGE knockdown. (3)RAGE knockdown partially reversed the promoted effect of cell proliferation, migration and invasion induced by HMGB1. Conclusion HMGB1 promotes the development and progression of CCRCC via ERK1/2 activation, which is partially mediated by RAGE.