Kruppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation by Up-regulating Keratin 13 Expression
Kruppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation by Up-regulating Keratin 13 Expression
复制标题
Kruppel样因子4通过上调角蛋白13表达促进食管鳞状细胞癌分化
DOI：
10.1074/jbc.m114.629717
复制
发表时间：
2015-05-22
影响因子：
4.8
通讯作者：
Liu, Zhihua
中科院分区：
文献类型：
--
作者：
He, Huan;Li, Sheng;Liu, Zhihua
鳞状细胞分化需要分化过程特异性基因的协调激活和抑制;该程序的中断伴随上皮的恶性转化。探索控制表皮增殖和终末分化的基因对更好地理解食管癌的发生至关重要。KLF 4是KLF家族转录因子的一员，参与细胞增殖和分化。本研究采用免疫组织化学方法分析食管鳞状细胞癌（ESCC）临床标本中KLF 4的表达，结果表明KLF 4的表达减少与低分化密切相关。此外，我们确定KLF 4和KRT 13的水平无疑增加了丁酸钠诱导的ESCC分化和G（1）期阻滞。相反，KLF 4和KRT 13的沉默消除了丁酸钠诱导的G（1）-S转换的抑制。分子生物学研究表明，KLF 4转录调控KRT 13，并且这两种分子在食管鳞癌组织和细胞系中的表达明显相关。总之，这些结果表明KLF 4转录调节KRT 13，并参与ESCC细胞分化。
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 KRT13levels 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.