High mobility group box 1 regulates tumor metastasis in cutaneous squamous cell carcinoma via the PI3K/AKT and MAPK signaling pathways.

Abstract

The present study examined the mechanisms of high mobility group box 1 (HMGB1)-induced cell migration in human cutaneous squamous cell carcinoma (CSCC) SCC13 cells. Western blotting, a chemotaxis assay and ELISA were performed to analyze HMGB1 level in SCC13 cells and its ability to regulate tumor metastasis. The results demonstrated a significantly higher level of HMGB1 in the SCC13 cell supernatant compared with the human epidermoid carcinoma A431 cell supernatant. Administration of HMGB1 to the SCC13 cells caused cell migration, which occurred in a time- and dose-dependent manner. Moreover, HMGB1 significantly activated the phosphosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways by an increased level of phosphorylation in p85PI3K, AKT, p38 and p42/44 MAPK. Taken together, these data suggest that HMGB1 regulates tumor metastasis in CSCC via the PI3K/AKT and MAPK signaling pathways.