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  • Year in Review
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CANCER METABOLISM IN 2018

Fuelling cancer cells

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

  • Lactate, not glucose, is a main carbon source for tricarboxylic acid (TCA) cycle oxidation in tumour cells1,2.

  • Leukaemic cells induce whole-body insulin resistance to increase glucose availability for their growth5.

  • Prostate cancer cells consume necrotic cell debris under both nutrient-replete and nutrient-depleted conditions6.

  • Many tumours become dependent on aspartate for continued growth in hypoxic environments7,8.

  • Asparagine is required for protein synthesis in glutamine-deprived conditions9 and promotes metastasis via epithelial–mesenchymal transition protein synthesis10.

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Fig. 1: Metabolic fuelling of cancer.

References

  1. Hui, S. et al. Glucose feeds the TCA cycle via circulating lactate. Nature 551, 115–118 (2017).

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  2. Faubert, B. et al. Lactate metabolism in human lung tumors. Cell 171, 358–371 (2017).

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  3. Corbet, C. et al. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Nat. Commun. 9, 1208 (2018).

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  9. Pavlova, N. N. et al. As extracellular glutamine levels decline, asparagine becomes an essential amino acid. Cell Metab. 27, 428–438 (2018).

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  10. Knott, S. R. V. et al. Asparagine bioavailability governs metastasis in a model of breast cancer. Nature 554, 378–381 (2018).

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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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Correspondence to Nissim Hay.

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The authors declare no competing interests.

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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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