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2019-10-01

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cc-by (c) Cano-Crespo, Sara et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/156737

Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression

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Recurs relacionat

https://doi.org/10.1038/s41598-019-50547-9

Resum

CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation.

Matèries

Aminoàcids, Cèl·lules canceroses

Matèries (anglès)

Amino acids, Cancer cells

Citació

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Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

Citació

CANO-CRESPO, Sara, et al. Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression. Scientific Reports. 2019. Vol. 9, num. 14065. ISSN 2045-2322. [consulted: 4 of August of 2026]. Available at: https://hdl.handle.net/2445/156737

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