Regulatory role of transcription factor HBP1 in anticancer efficacy of EGFR inhibitor erlotinib in HNSCC.

ABSTRACT

BACKGROUND: Epidermal growth factor receptor (EGFR) is often hyperactivated in head and neck squamous cell carcinoma (HNSCC); however, its downstream mediators are not fully identified. Here, we investigate the role of transcription factor HBP1 in the anticancer efficacy of EGFR inhibitor erlotinib in HNSCC. METHODS: The effect of erlotinib and HBP1 on cell proliferation and invasion was examined by flow cytometric analysis and a Matrigel invasion assay, respectively. Oral tumor specimens were used to evaluate the association between the expression level of EGFR and HBP1, and metastatic potential. RESULTS: Erlotinib caused cell growth arrest in the G1 phase and sluggish invasion with a concomitant increase in HBP1 and p27 expression. The erlotinib effect was attenuated upon HBP1 knockdown. Analysis of oral tumor specimens revealed that the low HBP1/high EGFR status can predict metastatic potential. CONCLUSIONS: Our data support HBP1 as a crucial mediator of EGFR-targeting inhibitors in HNSCC.