Krüppel-Like Factor 8 Is a New Wnt-Beta-Catenin Signaling Target Gene and Regulator in Hepatocellular CarcinomaReport as inadecuate




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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.



Author: Tian Yang , Sheng-Yun Cai , Jin Zhang , Jun-Hua Lu , Chuan Lin, Jian Zhai, Meng-Chao Wu , Feng Shen

Source: http://plos.srce.hr/



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