HMG box‐containing protein 1 (HBP1) as a downstream signaling effector of EGFR in oral cancer

Abstract

Aberrant activation of the epidermal growth factor (EGF) receptor (EGFR) signaling in the squamous cell carcinomas of the head and neck (SCCHN) is often associated with inauspicious prognosis and low survival. Transcription factor HMG box‐containing protein 1 (HBP1) functions as a potential tumor repressor in various cancers; however, its role in oral cancer is still unclear. Analysis of human oral cancer specimens revealed that the mean HBP1 mRNA level in tumors was significantly lower than that of the normal tissues, and that the concurrent status of low HBP1 and high EGFR was associated with the invasiveness of oral cancer. To explore the potential link between EGFR signaling and HBP1, we treated EGFR‐overexpressing oral cancer cell lines, HSC‐3 and FaDu, with EGFR inhibitors, AG1478 and Erlotinib, or EGFR siRNA, and found that EGFR down‐regulation increased HBP1 expression. Administration of phosphatidylinositol 3‐kinase (PI3K) inhibitor, Ly294002, decreased Akt phosphorylation and increased HBP1 expression. Overall, the expression of Akt and HBP1 acted in a reciprocal manner. Moreover, HBP1 knockdown in HSC‐3 cells enhanced in vitro colony formation and in vivo xenograft tumor growth. HBP1 knockdown attenuated Erlotinib‐mediated cyclin D1 reduction and subsequent G1 arrest. Together, our data reveal a novel role of HBP1 as a downstream effector of the EGFR/Akt signaling pathway in oral cancer.