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

Head Neck. 2020 Oct;42(10):2958-2967. doi: 10.1002/hed.26346. Epub 2020 Jul 17.

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.

Keywords: EGFR; HBP1; HNSCC; erlotinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / pharmacology
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / genetics
  • High Mobility Group Proteins
  • Humans
  • Repressor Proteins
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Transcription Factors

Substances

  • HBP1 protein, human
  • High Mobility Group Proteins
  • Repressor Proteins
  • Transcription Factors
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors