Metabolomics

Dataset Information

6

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


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 PFKP (phosphofructokinase, platelet), 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.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 PFKP (phosphofructokinase, platelet), 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.

INSTRUMENT(S): Varian, Bruker

SUBMITTER: Jueun Lee  

PROVIDER: MTBLS387 | MetaboLights | 2017-11-07

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS387 Other
Items per page:
1 - 1 of 1
altmetric image

Publications


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  ...[more]

Similar Datasets

2017-01-01 | S-EPMC5309788 | BioStudies
1000-01-01 | S-EPMC4998991 | BioStudies
1000-01-01 | S-EPMC5523067 | BioStudies
2020-01-01 | S-EPMC7407102 | BioStudies
1000-01-01 | S-EPMC4537021 | BioStudies
2019-01-01 | S-EPMC6779746 | BioStudies
2011-01-01 | S-EPMC3110666 | BioStudies
2012-01-01 | S-EPMC3670098 | BioStudies
1000-01-01 | S-EPMC4498084 | BioStudies
2013-01-01 | S-EPMC3696551 | BioStudies