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Cellular and Molecular Biology

Comment on: “Evolving roles of CD38 metabolism in solid tumour microenvironment”

British Journal of Cancer volume 128, page 491 (2023)Cite this article

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In their paper, Gao et al. discuss the widely accepted idea of the major role that CD38 ectonucleotidase plays in the tumour microenvironment [1]. They mention the regulation mechanisms of CD38 enzymatic activity with a specific reference to Zocchi et al. [2] to support their statement about ATP-mediated suppression of cADPR hydrolysis. However, the referenced manuscript does not contain any convincing evidence of CD38 hydrolase inhibition by ATP. Meanwhile, Takasawa et al. indeed have demonstrated that ATP inhibited the cADPR hydrolase activity which resulted in the accumulation of cADPR [3]. Further studies confirmed this observation and provided insights into the mechanism for competitive binding of ATP to the cADPR-binding site of CD38 [4] to put forward a model for a cADPR-mediated signalling system in pancreatic islet β-cells [5]. Based on this model, extensively reviewed in [6], ATP-binding leads to the accumulation of cADPR. Given all the above, ATP serves as a competitive inhibitor of cADPR hydrolysis and, while having no influence on CD38 cyclase activity, facilitates the accumulation of cADPR.

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References

  1. Gao L, Du X, Li J, Xiao-Feng Qin F. Evolving roles of CD38 metabolism in solid tumour microenvironment. Br J Cancer. 2022. https://doi.org/10.1038/s41416-022-02052-6.

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  1. Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Pavel Nesmiyanov

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  1. Pavel Nesmiyanov
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Correspondence to Pavel Nesmiyanov.

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Nesmiyanov, P. Comment on: “Evolving roles of CD38 metabolism in solid tumour microenvironment”. Br J Cancer 128, 491 (2023). https://doi.org/10.1038/s41416-022-02113-w

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