title: Krüppel-like factor 4 (KLF4) activates the transcription of the gene for the platelet isoform of phosphofructokinase (PFKP) in breast cancer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Moon
authors.forename: Hee Eun
authors.initials: HE
authors.lastname: Kim
authors.forename: Eunjin
authors.initials: E
authors.lastname: Koh
authors.forename: Se Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Won-Ji
authors.initials: WJ
authors.lastname: Jin
authors.forename: Byeong-Woo
authors.initials: BW
authors.lastname: Park
authors.forename: Sahng Wook
authors.initials: SW
authors.lastname: Park
authors.forename: Kyung-Sup
authors.initials: KS
authors.lastname: Kim
mesh_terms: D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D025502:Phosphofructokinase-1, Type C / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D019344:Lactic Acid; D025502:Phosphofructokinase-1, Type C; D005947:Glucose