1. Institute of Biochemistry, Microbiology, and Immunology, Chung Shan Medical University, Taichung, Taiwan;
2. Clinical Laboratory, Chung Shan Medical University Hospital Taichung, Taiwan;
3. Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan;
4. Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan;
5. School of Medicine, National Yang Ming University, Taipei, Taiwan;
6. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan;
7. School of Medicine, Chung Shan Medical University, Taichuang, Taiwan;
8. Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan;
9. Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan;
10. Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan;
11. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan;
12. Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan.
* These authors contributed equally.
Krüppel-like factors can bind to specific DNA motifs and regulate various cellular functions, such as metabolism, cell proliferation, and differentiation. Krüppel-like factor 6 (KLF6), a member of this family, is downregulated in human cancers. Oral cancer is a highly prevalent type in Taiwan. Although KLF6 overexpression in human cancer cells inhibits cell proliferation, induces apoptosis, and attenuates cell migration, the effects of KLF6 on oral cancer remains poorly elucidated. This study investigated the role of KLF6 in oral cancer tumorigenesis. Immunohistochemical staining revealed that nuclear KLF6 level was significantly and inversely associated with tumor size and stages. KLF6 overexpression attenuated the migration and invasion of oral cancer SAS cells. Zymography assay demonstrated that KLF6 inhibited the activities of matrix metalloproteinase 9 (MMP-9) and weakened the expression of mesenchymal markers, such as snail, slug, and vimentin. Our study is the first to provide demonstrate that KLF6 functions as a tumor suppressor gene and prevents the metastasis of oral cancer cells.
Keywords: kruppel-like factor 6 (KLF6), oral cancer, migration, matrix metalloproteinase 9.