Kruppel like factor 4 promotes esophageal squamous cell carcinoma differentiation by upregulating keratin 13 expression [Gene Regulation]

April 7th, 2015 by He, H., Li, S., Hong, Y., Zou, H., Chen, H., Ding, F., Wan, Y., Liu, Z.

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 which 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 involved in both cellular proliferation and differentiation. The present study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) exhibited that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 level were undoubtedly augmented upon sodium butyrate (SB) induced ESCC differentiation and G1-phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced by SB. 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 involves in ESCC cell differentiation.