A Positive Feedback Loop Between Myc and Aerobic Glycolysis Sustains Tumor Growth in a Drosophila Tumor Model

Resource type
Date created
2019-07-17
Authors/Contributors
Abstract
Cancer cells usually exhibit aberrant cell signaling and metabolic reprogramming. However, mechanisms of crosstalk between these processes remain elusive. Here, we show that in an in vivo tumor model expressing oncogenic Drosophila Homeodomain-interacting protein kinase (Hipk), tumor cells display elevated aerobic glycolysis. Mechanistically, elevated Hipk drives transcriptional upregulation of Drosophila Myc (dMyc; MYC in vertebrates) likely through convergence of multiple perturbed signaling cascades. dMyc induces robust expression of pfk2 (encoding 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase; PFKFB in vertebrates) among other glycolytic genes. Pfk2 catalyzes the synthesis of fructose-2,6-bisphosphate, which acts as a potent allosteric activator of Phosphofructokinase (Pfk) and thus stimulates glycolysis. Pfk2 and Pfk in turn are required to sustain dMyc protein accumulation post-transcriptionally, establishing a positive feedback loop. Disruption of the loop abrogates tumorous growth. Together, our study demonstrates a reciprocal stimulation of Myc and aerobic glycolysis and identifies the Pfk2-Pfk governed committed step of glycolysis as a metabolic vulnerability during tumorigenesis.
Document
Published as
Wong, K. K. L., Liao, J. Z., & Verheyen, E. M. (2019). A positive feedback loop between Myc and aerobic glycolysis sustains tumor growth in a Drosophila tumor model. ELife, 8. DOI: 10.7554/eLife.46315.
Publication title
ELife
Document title
A Positive Feedback Loop Between Myc and Aerobic Glycolysis Sustains Tumor Growth in a Drosophila Tumor Model
Date
2019
Volume
8
Publisher DOI
10.7554/eLife.46315
Copyright statement
Copyright is held by the author(s).
Peer reviewed?
No
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Member of collection
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elife-46315-v2.pdf 4.27 MB