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

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 Ryu, Sunghyouk Park, Jae-Ho Cheong, Sang Won Kang, Soo-Youl Kim, Geum-Sook Hwang (), Jong In Yook () and Hyun Sil Kim ()
Additional contact information
Nam Hee Kim: Oral Cancer Research Institute, Yonsei University College of Dentistry
Yong Hoon Cha: Oral Cancer Research Institute, Yonsei University College of Dentistry
Jueun Lee: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute
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
Miso Nam: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute
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

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14374

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