Metformin disrupts malignant behavior of oral squamous cell carcinoma via a novel signaling involving Late SV40 factor/Aurora-A

• Published in: Scientific Reports Vol. 7; no. 1; pp. 1358 - 15
• Main Authors: Chen, Chang-Han, Tsai, Hsin-Ting, Chuang, Hui-Ching, Shiu, Li-Yen, Su, Li-Jen, Chiu, Tai-Jan, Luo, Sheng-Dean, Fang, Fu-Min, Huang, Chao-Cheng, Chien, Chih-Yen
• Format: Journal Article
• Language: English
• Published: London Springer Science and Business Media LLC 02.05.2017; Nature Publishing Group UK; Nature Publishing Group; Nature Portfolio
• Subjects: 13/105; 13/109; 13/51; 13/89; 13/95; 14/19; 631/67/1536; 64/60; 692/4028/67; 96/1; Antidiabetics; Antineoplastic Agents; Aurora Kinase A; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; DNA-Binding Proteins; Down-Regulation; Humanities and Social Sciences; Humans; Malignancy; Medicine; Metastases; Metformin; Mouth Neoplasms; multidisciplinary; Oral cancer; Oral squamous cell carcinoma; Q; R; Science; Science (multidisciplinary); Signal Transduction; Squamous cell carcinoma; Survival; Transcription Factors; Tumorigenesis; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-01353-8

Conventional therapeutic processes in patient with OSCC are associated with several unfavorable effects leading to patients with poor survival rate. Metformin has been shown to protect against a variety of specific diseases, including cancer. However, the precise roles and mechanisms underlying the therapeutic effects of metformin on OSCC remain elusive. In the current study, in vitro and xenograft model experiments revealed that metformin inhibited growth and metastasis of oral cancer cells. Importantly, metformin-restrained tumorigenesis of oral cancer was accompanied with strong decrease of both Aurora-A and Late SV40 Factor (LSF) expressions. Furthermore, LSF contributed to Aurora-A-elicited malignancy behaviors of oral cancer via binding to the promoter region of Aurora-A. A significant correlation was observed between LSF and Aurora-A levels in a cohort of specimens of oral cancer. These findings showed that a novel LSF/Aurora-A-signaling inhibition supports the rationale of using metformin as potential OSCC therapeutics.