Krüppel-like factor 8 is a new Wnt/beta-catenin signaling target gene and regulator in hepatocellular carcinoma.
Krüppel-like factor 8 is a new Wnt/beta-catenin signaling target gene and regulator in hepatocellular carcinoma.
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DOI：
10.1371/journal.pone.0039668
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shen F
中科院分区：
文献类型：
--
作者：
Yang T;Cai SY;Zhang J;Lu JH;Lin C;Zhai J;Wu MC;Shen F
Krüppel-like factor 8 (KLF8) plays important role in cell cycle and oncogenic transformation. Here we report the mechanisms by which KLF8 crosstalks with Wnt/β-catenin signaling pathway and regulates hepatocellular carcinoma (HCC) cells proliferation. We show that overexpression of KLF8 and nucleus accumulation of β-catenin in the human HCC samples are positively correlated. More importantly, KLF8 protein levels plus nucleus accumulation of β-catenin levels were significantly elevated in high-grade HCC compared to low-grade HCC. Using HCC HepG2 cells we find that, on the one hand both protein and mRNA of KLF8 are up-regulated under Wnt3a stimulation, on the other hand overexpression of KLF8 increases the cytoplasm and nucleus accumulation of β-catenin, recruits p300 to β-catenin/T-cell factor 4 (TCF4) transcription complex, enhances TOP flash report gene transcription, and induces Wnt/β-catenin signaling target genes c-Myc, cyclin D1 and Axin1 expression. Knockdown of KLF8 using shRNA inhibits Wnt3a induced transcription of TOP flash report gene and expression of c-Myc, cyclin D1 and Axin1. Knockdown of β-catenin by shRNA rescues the enhanced HepG2 and Hep3B cells proliferation ability induced by overexpression of KLF8.
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