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

Authors
 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  ;  Hyun Sil Kim 
Citation
 Nature Communications, Vol.8 : 14374, 2017 
Journal Title
 Nature Communications 
Issue Date
2017
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.
Files in This Item:
T201700338.pdf Download
DOI
10.1038/ncomms14374
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Ryu, Joo Kyung(류주경)
Yang, Ji Hye(양지혜)
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Lee, Yoon Mi(이윤미)
Zhang, Xiang Lan(장향란)
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Cho, Eunae(조은애산드라) ORCID logo https://orcid.org/0000-0002-0820-3019
Cha, So Young(차소영) ORCID logo https://orcid.org/0000-0002-2810-3883
Cha, Yong Hoon(차용훈) ORCID logo https://orcid.org/0000-0003-1761-3260
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/153577
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