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CELL MOTILITY

Endothelial metabolism going single

Nature Metabolism volume 3, pages 593–594 (2021)Cite this article

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Endothelial cell migration is indispensable for (tumour) angiogenesis and is fuelled by glycolysis. The metabolic underpinnings have been only partially unravelled to date, partly because of the lack of appropriate tools to analyse metabolic flux at the single-cell level. In this issue, Wu et al. introduce a novel imaging assay to capture glycolytic flux during motion in single endothelial cells. With this new tool, the authors uncovered a glycolysis-driven cytoskeletal remodelling apparatus that propels endothelial cell motility.

Angiogenesis, the formation of blood vessels, is a hallmark of cancer, and blocking this process is a therapeutic goal. However, current anti-angiogenic therapies based on blocking a single pro-angiogenic molecule (such as the growth factor VEGF) are limited by insufficient efficacy and resistance, partly because tumours upregulate additional angiogenic signals. Targeting endothelial cell (EC) metabolism, on which angiogenic signals converge, has emerged as an alternative strategy for anti-angiogenic therapy1. Studies have documented that ECs rely primarily on glycolysis to generate most of their ATP for actin cytoskeletal remodelling, a process necessary for EC motility during angiogenesis2. However, metabolic flux data at the cellular and subcellular levels were lacking. By developing a novel sensor of a glycolytic end product (lactate) with sensitivity at the cellular and subcellular levels (as a surrogate marker of glycolytic flux), Wu et al., in this issue of Nature Metabolism, report that glycolytic production of ATP is indeed necessary for the local actin cytoskeleton remodelling required for EC motility3. Their study also provides evidence of how angiogenic stimuli use EC metabolism (specifically glycolysis) to generate ATP for the phosphorylation of key actin cytoskeletal regulators. The development of such metabolite sensors heralds a new future for studying cell metabolism, including that of ECs, at the cellular or subcellular level.

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Fig. 1: Glycolysis-driven cytoskeletal remodelling during endothelial cell migration.

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Acknowledgements

P.C. is supported by grants from Methusalem funding (Flemish government), the Fund for Scientific Research-Flanders (FWO-Vlaanderen) and the European Research Council (ERC Advanced Research Grant EU- ERC743074); L.M.B. is supported by a Marie-Curie fellowship. The authors thank M. Dewerchin for help with the manuscript.

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Authors and Affiliations

  1. Laboratory of Angiogenesis & Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium

    Abhishek Subramanian, Lisa M. Becker & Peter Carmeliet

  2. Laboratory of Angiogenesis & Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium

    Abhishek Subramanian, Lisa M. Becker & Peter Carmeliet

  3. Laboratory of Angiogenesis & Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Peter Carmeliet

  4. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China

    Peter Carmeliet

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  1. Abhishek Subramanian
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  2. Lisa M. Becker
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  3. Peter Carmeliet
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Correspondence to Peter Carmeliet.

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P.C. is named as an inventor on patent applications claiming subject matter related to results described in this article. The other authors declare no competing interests.

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Subramanian, A., Becker, L.M. & Carmeliet, P. Endothelial metabolism going single. Nat Metab 3, 593–594 (2021). https://doi.org/10.1038/s42255-021-00399-3

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