Krüppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation by Up-regulating Keratin 13 Expression

Squamous cell differentiation requires the coordinated activation and repression of genes specific to the differentiation process; disruption of this program accompanies malignant transformation of epithelium. The exploration of genes that control epidermal proliferation and terminal differentiation is vital to better understand esophageal carcinogenesis. KLF4 is a member of the KLF family of transcription factors and is involved in both cellular proliferation and differentiation. This study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) demonstrated that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 levels were undoubtedly augmented upon sodium butyrate-induced ESCC differentiation and G 1 phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G 1 -S transition induced by sodium butyrate. Molecular investigation demonstrated that KLF4 transcriptionally regulated KRT13 and the expression of the two molecules appreciably correlated in ESCC tissues and cell lines. Collectively, these results suggest that KLF4 transcriptionally regulates KRT13 and is invovled in ESCC cell differentiation. Background: The transcriptional regulation of keratin (KRT) 13 and its underlying mechanism has not been fully elucidated. Results: Up-regulation of KRT13 by Krüppel-like factor 4 (KLF4) is mediated through GKRE in the KRT13 promoter. Conclusion: KLF4 induces differentiation of ESCC by promoting KRT13 transcription. Significance: KLF4 plays a significant and previously unrecognized role in regulation of KRT13 and cell differentiation.