EC GNG metabolism · Endothelial Gluconeogenesis: a novel target for tumor anti-angiogenesis?
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-01-01 → 2019-02-13
- EU contribution
- €172,800
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Endothelial Gluconeogenesis: a novel target for tumor anti-angiogenesis?
Before the start of the funded Marie Curie project, the host lab had recently reported that endothelial cell (EC) metabolism (glycolysis and fatty acid) is crucial to control vessel sprouting, a process which is deregulated in several pathologies including cancer. Similar to cancer cells, endothelial cells are "glycolysis-addicted" and highly dependent on this pathway to produce the required energy for sprouting into avascular areas, where glucose becomes limiting. The overall project hypothesis aimed to investigate endothelial metabolism into more detail, and to discover new pathways driving sprouting angiogenesis. Besides, we also evaluated whether ECs could produce glycolytic intermediates de-novo via a process called gluconeogenesis (GNG). Finally, as metabolism of tumor endothelial cells (TECs) is largely unknown, we investigated their properties in order to improve current anti-angiogenic therapies.
Data: CORDIS, © European Union
Project objective
Angiogenesis promotes tumor progression and metastasis; unfortunately current anti-angiogenic strategies targeting endothelial growth factors suffer from limited efficacy and toxicity. The host laboratory pioneered the novel concept that blood vessel forming endothelial cells (ECs) reprogram their metabolism to become glucose-addicted and rely on glycolysis to generate ATP required for angiogenesis. Furthermore, to increase biomass production and maintain redox homeostasis, ECs shunt glycolytic intermediates into glycolysis side-pathways. Further ECs diverge from pre-existing blood vessel into avascular tissue, the scarcer external glucose levels will become. Currently, how ECs maintain the generation of glycolytic intermediates under such conditions remains unknown. One possibility is the de-novo synthesis of these intermediates through gluconeogenesis (GNG).To date, nothing is known about GNG metabolism in ECs, which underscores the novelty of my proposal. GNG is particularly interesting since preliminary findings indicate that ECs express all enzymes involved in GNG, and impairing this pathway decreases EC proliferation and sprouting. Therefore, through a multi-angled approach, I will unravel the role of GNG in ECs and uncover its contribution to blood vessel sprouting both in normal and pathological angiogenesis. Ultimately this project will explore whether blocking GNG may inhibit pathological angiogenesis (e.g. cancer) and translate my findings into therapeutic strategies.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union