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Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress

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Listed:
  • Nam Hee Kim

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Yong Hoon Cha

    (Oral Cancer Research Institute, Yonsei University College of Dentistry
    Present address: Department of Oral and Maxillofacial Surgery, Yonsei University College of Dentistry, Seoul 120-752, Korea.)

  • Jueun Lee

    (Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute
    Sungkyunkwan University)

  • Seon-Hyeong Lee

    (Cancer Cell and Molecular Biology Branch, National Cancer Center)

  • Ji Hye Yang

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Jun Seop Yun

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Eunae Sandra Cho

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Xianglan Zhang

    (Oral Cancer Research Institute, Yonsei University College of Dentistry
    Yanbian University Medical College)

  • Miso Nam

    (Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute
    Sungkyunkwan University)

  • Nami Kim

    (Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute)

  • Young-Su Yuk

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • So Young Cha

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Yoonmi Lee

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Joo Kyung Ryu

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Sunghyouk Park

    (College of Pharmacy, Natural Product Research Institute, Seoul National University)

  • Jae-Ho Cheong

    (Yonsei University College of Medicine)

  • Sang Won Kang

    (Research Center for Cell Homeostasis, Ewha Womans University)

  • Soo-Youl Kim

    (Cancer Cell and Molecular Biology Branch, National Cancer Center)

  • Geum-Sook Hwang

    (Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute)

  • Jong In Yook

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

  • Hyun Sil Kim

    (Oral Cancer Research Institute, Yonsei University College of Dentistry)

Abstract

Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial–mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.

Suggested Citation

  • Nam Hee Kim & Yong Hoon Cha & Jueun Lee & Seon-Hyeong Lee & Ji Hye Yang & Jun Seop Yun & Eunae Sandra Cho & Xianglan Zhang & Miso Nam & Nami Kim & Young-Su Yuk & So Young Cha & Yoonmi Lee & Joo Kyung , 2017. "Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14374
    DOI: 10.1038/ncomms14374
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