Cancer cells consume and utilize glucose at a higher rate than normal cells. However, some microenvironments limit the availability of nutrients and glucose. In 2018, researchers found that tumours depend on a variety of different nutrient sources, both locally and systemically, to overcome metabolic limitations and promote tumour progression and metastasis.
Key advances
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Lactate, not glucose, is a main carbon source for tricarboxylic acid (TCA) cycle oxidation in tumour cells1,2.
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Leukaemic cells induce whole-body insulin resistance to increase glucose availability for their growth5.
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Prostate cancer cells consume necrotic cell debris under both nutrient-replete and nutrient-depleted conditions6.
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Many tumours become dependent on aspartate for continued growth in hypoxic environments7,8.
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Asparagine is required for protein synthesis in glutamine-deprived conditions9 and promotes metastasis via epithelial–mesenchymal transition protein synthesis10.
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References
Hui, S. et al. Glucose feeds the TCA cycle via circulating lactate. Nature 551, 115–118 (2017).
Faubert, B. et al. Lactate metabolism in human lung tumors. Cell 171, 358–371 (2017).
Corbet, C. et al. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Nat. Commun. 9, 1208 (2018).
Chen, Y.-J. et al. Lactate metabolism is associated with mammalian mitochondria. Nat. Chem. Biol. 12, 937–943 (2016).
Ye, H. et al. Subversion of systemic glucose metabolism as a mechanism to support the growth of leukemia cells. Cancer Cell 34, 659–673 (2018).
Kim, S. M. et al. PTEN deficiency and AMPK activation promote nutrient scavenging and anabolism in prostate cancer cells. Cancer Discov. 8, 866–883 (2018).
Garcia-Bermudez, J. et al. Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. Nat. Cell Biol. 20, 775–781 (2018).
Sullivan, L. B. et al. Aspartate is an endogenous metabolic limitation for tumour growth. Nat. Cell Biol. 20, 782–788 (2018).
Pavlova, N. N. et al. As extracellular glutamine levels decline, asparagine becomes an essential amino acid. Cell Metab. 27, 428–438 (2018).
Knott, S. R. V. et al. Asparagine bioavailability governs metastasis in a model of breast cancer. Nature 554, 378–381 (2018).
Acknowledgements
The authors’ research is supported by NIH grants R01AG016927, R01CA090764 and R01CA206167 (N.H.), by VA grant BX000733 (N.H.) and by F30CA225058 NIH award (A.R.T.).
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Terry, A.R., Hay, N. Fuelling cancer cells. Nat Rev Endocrinol 15, 71–72 (2019). https://doi.org/10.1038/s41574-018-0146-6
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DOI: https://doi.org/10.1038/s41574-018-0146-6
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