Kruppel-like Factor 4 (KLF4) Activates the Transcription of the Gene for the Platelet Isoform of Phosphofructokinase (PFKP) in Breast Cancer
Kruppel-like Factor 4 (KLF4) Activates the Transcription of the Gene for the Platelet Isoform of Phosphofructokinase (PFKP) in Breast Cancer
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DOI：
10.1074/jbc.m111.236737
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发表时间：
2011-07-08
影响因子：
4.8
通讯作者：
Kim, Kyung-Sup
中科院分区：
文献类型：
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作者：
Moon, Jong-Seok;Kim, Hee Eun;Kim, Kyung-Sup
Kruppel 样因子 4 (KLF4) 是一种转录因子，在细胞分化、增殖和存活中发挥重要作用，尤其是在癌症中。这项研究表明，KLF4 通过上调磷酸果糖激酶 (PFKP) 的血小板亚型来激活乳腺癌细胞中的糖酵解代谢。 KLF4通过直接结合PFKP启动子来激活PFKP基因的转录。敲低 KLF4 会抑制葡萄糖摄取和乳酸生成，但过表达 KLF4 则会激活它们。与 PFKP 不同，磷酸果糖激酶和糖酵解基因的其他亚型的表达不受 KLF4 的影响。人类乳腺癌组织中KLF4和PFKP的表达密切相关。这项研究还表明，PFKP 在乳腺癌细胞的细胞增殖中发挥着关键作用。总之，KLF4通过转录激活乳腺癌细胞中的PFKP基因在维持高糖酵解代谢中发挥作用。
Kruppel-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.