Androgen receptor promotes oral squamous cell carcinoma cell migration by increasing EGFR phosphorylation

Abstract

Xin Liu,1 Shanglan Qing,2 Keke Che,3 Lihua Li,4 Xiaoming Liao51Department of General Dentistry, Chongqing Savaid Stomatology Hospital, University of Chinese Academy of Sciences, Chongqing 400014, People’s Republic of China; 2Department of Stomatology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400014, People’s Republic of China; 3Department of Pharmacology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400014, People’s Republic of China; 4Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, People’s Republic of China; 5Department of Stomatology, Chongqing Prevention and Treatment Hospital for Occupational Diseases, Chongqing 400060, People’s Republic of ChinaObjectives: This study is aimed to investigate the role of androgen receptor (AR) in regulating oral squamous cell carcinoma (OSCC) cells migration.Materials and methods: Tumors from 23 patients with OSCC and five OSCC cell lines were used for analyzing AR expression. The effects of AR agonist and antagonist were used to examine the role of AR in regulating the migration of OSCC cells.Results: Ten of 23 tumors from patients with OSCC were AR positive. There was no significant difference in total EGFR (tEGFR) expression between AR-positive tumors and AR-negative tumors. However, the expression of phosphorylated EGFR (pEGFR) in AR-positive tumors was significantly higher than that in AR-negative tumors (p<0.01). Stimulation of AR by dihydrotestosterone in SCC9 (AR-positive OSCC cell) caused an increase in pEGFR and pAKT expression and promoted cell migration without changed tEGFR expression, whereas treatment with bicalutamide led to a decrement in pEGFR expression and pAKT and inhibited cell migration. No effects were found in SCC25 cell line (AR-negative) either treated by dihydrotestosterone or bicalutamide. Furthermore, SCC9 cell line treated by EGF or cetuximab (EGFR inhibitor) significantly promoted or inhibited cell migration.Conclusion: Our data indicate that OSSC tumors and OSCC cell lines express AR which is critical for promoting cell migration by increasing EGFR phosphorylation.Keywords: oral squamous cell carcinoma, androgen receptor, EGFR, migration, phosphorylation

Keywords

• oral squamous cell carcinoma
• androgen receptor
• EGFR
• migration
• phosphorylation