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Krüppel-like Factor 4 (KLF4) Activates the Transcription of the Gene for the Platelet Isoform of Phosphofructokinase (PFKP) in Breast Cancer

作者:Jong‐Seok Moon, Hee‐Eun Kim, Eunjin Koh, Seho Park, Won-Ji Jin, Byeong‐Woo Park, Sahng Wook Park, Kyung‐Sup Kim · 发表于:Journal of Biological Chemistry · 年份:2011 · DOI:10.1074/jbc.m111.236737 · 被引用次数:149 · 研究领域:Kruppel-like factors research、Cancer-related gene regulation、Genetic Syndromes and Imprinting

Krüppel-like factor 4 (KLF4) is a transcription factor that plays an important role in cell differentiation, proliferation, and survival, especially in the context of cancers. This study revealed that KLF4 activates glycolytic metabolism in breast cancer cells by up-regulating the platelet isoform of phosphofructokinase (PFKP). KLF4 activated the transcription of the PFKP gene by directly binding to the PFKP promoter. Whereas glucose uptake and lactate production were inhibited by the knockdown of KLF4, they were activated by the overexpression of KLF4. Unlike PFKP, the expressions of the other isoforms of phosphofructokinase and glycolytic genes were unaffected by KLF4. The human breast cancer tissues showed a close correlation between KLF4 and PFKP expression. This study also showed that PFKP plays a critical role in cell proliferation in breast cancer cells. In conclusion, it is suggested that KLF4 plays a role in maintenance of high glycolytic metabolism by transcriptional activation of the PFKP gene in breast cancer cells.