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Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton
Open accessAbstract
Summary The Phosphoinositide 3-Kinase (PI3K) pathway regulates multiple steps in glucose metabolism but also cytoskeletal functions, such as cell movement and attachment. Here we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A and an increase in aldolase activity. Consistently, PI3K-, but not AKT-, SGK- or mTOR-inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point towards a master regulatory function of PI3K that integrates an epithelial cell’s metabolism and its form, shape and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling.
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The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
Self-citationPhosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120
Self-citationImaging cytosolic NADH-NAD(+) redox state with a genetically encoded fluorescent biosensor
Hung, Y. P., Albeck, J. G., Tantama, M., & Yellen, G. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.012 · Cited by 509
Cited by
The PI3K Pathway in Human Disease
Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017) · Cell · doi:10.1016/j.cell.2017.07.029 · Cited by 2,749
Self-citationThe PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
Targeting PI3K/Akt signal transduction for cancer therapy
He, Y., Sun, M. M., Zhang, G. G., Yang, J., Chen, K. S., Xu, W. W., & Li, B. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00828-5 · Cited by 1,892
Lactate Metabolism in Human Lung Tumors
Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.019 · Cited by 1,343
Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy?
Hay, N. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.77 · Cited by 1,115
Metadata
- Authors
- Hu, H., Juvekar, A., Lyssiotis, C. A., Lien, E. C., Albeck, J. G., Oh, D., Varma, G., Hung, Y. P., Ullas, S., Lauring, J., Seth, P., Lundquist, M. R., Tolan, D. R., Grant, A. K., Needleman, D. J., Asara, J. M., Cantley, L. C., & Wulf, G. M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 164
- Issue
- 3
- Pages
- 433-446
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2254906934
- Cited by
- 380
- References
- 3
- FWCI
- 15.50
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hu, H., Juvekar, A., Lyssiotis, C. A., Lien, E. C., Albeck, J. G., Oh, D., Varma, G., Hung, Y. P., Ullas, S., Lauring, J., Seth, P., Lundquist, M. R., Tolan, D. R., Grant, A. K., Needleman, D. J., Asara, J. M., Cantley, L. C., & Wulf, G. M. (2016). Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton. Cell. https://doi.org/10.1016/j.cell.2015.12.042
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
