The Janus-faced roles of Krüppel-like factor 4 in oral squamous cell carcinoma cells
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Wenwen Li1,*, Man Liu1,*, Ying Su1, Xinying Zhou1, Yao Liu1, Xinyan Zhang1
1Beijing Institute of Dental Research, Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China
*These authors have contributed equally to this work
Xinyan Zhang, e-mail: [email protected]
Keywords: KLF4, tumor suppressor, oncogene, oral squamous cell carcinoma
Received: May 10, 2015 Accepted: October 21, 2015 Published: October 28, 2015
Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that regulates many essential processes, including development and cell differentiation, proliferation, and apoptosis. Along with these roles in normal cells and tissues, KLF4 has important tumor suppressive and oncogenic functions in some malignancies. However, the roles of KLF4 in oral squamous cell carcinoma remain unclear. This study investigated the epigenetic alterations and possible roles of KLF4 in oral cancer carcinogenesis. Notably, KLF4 expression was significantly decreased in human oral cancer tissues compared with healthy controls, and KLF4 promoter hypermethylation contributed to the suppression of KLF4 expression. KLF4 expression was associated with tumor grade. Its expression was much lower in poorly differentiated oral cancers than in well-differentiated cancer cells. KLF4 exerted its antitumor activity in vitro and/or in vivo by inhibiting cell proliferation, cell cycle progression, cell colony formation and by inducing apoptosis. In addition, KLF4 over-expression promoted oral cancer cell migration and invasion in vitro. Knockdown of KLF4 promoted oral cancer cells growth and colony formation, and simultaneously inhibited cell migration and invasion. Mechanistic studies revealed that MMP-9 might contribute to KLF4-mediated cell migration and invasion. These results provide evidence that KLF4 might play Janus-faced roles in oral cancer carcinogenesis, acting both as a tumor suppressor and as an oncogene.
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