Krüppel 样因子 4（KLF4）激活乳腺癌中磷酸果糖激酶同工酶（PFKP）基因的转录。
Krüppel-like factor 4 (KLF4) activates the transcription of the gene for the platelet isoform of phosphofructokinase (PFKP) in breast cancer.
机构信息
Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Brain Korea 21 Project for Medical Science, Yonsei University, College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea.
出版信息
J Biol Chem. 2011 Jul 8;286(27):23808-16. doi: 10.1074/jbc.M111.236737. Epub 2011 May 17.
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.
Krüppel 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。本研究揭示，KLF4 通过上调磷酸果糖激酶（PFKP）的血小板同工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，而过表达 KLF4 则会激活它们。与 PFKP 不同，其他同工型的磷酸果糖激酶和糖酵解基因的表达不受 KLF4 影响。人乳腺癌组织中 KLF4 和 PFKP 的表达密切相关。本研究还表明，PFKP 在乳腺癌细胞的增殖中起关键作用。综上所述，本研究提示 KLF4 通过转录激活 PFKP 基因在乳腺癌细胞中维持高糖酵解代谢。
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