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 YookHyun Sil Kim

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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.

Original languageEnglish
Article number14374
JournalNature communications
Volume8
DOIs
Publication statusPublished - 2017 Feb 8

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF-2012M3A9B2052523, NRF-2014R1A2A1A05004670, NRF-2016R1E1A1A01942724) funded by the Korea government (MSIP), a grant from the National Research Foundation of Korea (NRF-2014R1A6A3A04055110) funded by the Korea government (MOE), and a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (1420310). This work was also supported by the by the National Research Council of Science & Technology (CAP-2012-2-KBSI), and the Korea Basic Science Institute (C36705). S.Y. Kim was supported by a grant from the National Cancer Center of Korea (NCC1410670).

Publisher Copyright:
© The Author(s) 2017.

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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