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The V-ATPases in cancer and cell death

Cancer Gene Therapy volume 29, pages 1529–1541 (2022)Cite this article

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Abstract

Transmembrane ATPases are membrane-bound enzyme complexes and ion transporters that can be divided into F-, V-, and A-ATPases according to their structure. The V-ATPases, also known as H+-ATPases, are large multi-subunit protein complexes composed of a peripheral ___domain (V1) responsible for the hydrolysis of ATP and a membrane-integrated ___domain (V0) that transports protons across plasma membrane or organelle membrane. V-ATPases play a fundamental role in maintaining pH homeostasis through lysosomal acidification and are involved in modulating various physiological and pathological processes, such as macropinocytosis, autophagy, cell invasion, and cell death (e.g., apoptosis, anoikis, alkaliptosis, ferroptosis, and lysosome-dependent cell death). In addition to participating in embryonic development, V-ATPase pathways, when dysfunctional, are implicated in human diseases, such as neurodegenerative diseases, osteopetrosis, distal renal tubular acidosis, and cancer. In this review, we summarize the structure and regulation of isoforms of V-ATPase subunits and discuss their context-dependent roles in cancer biology and cell death. Updated knowledge about V-ATPases may enable us to design new anticancer drugs or strategies.

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Fig. 1: Structure and mechanism of V-ATPase.
Fig. 2: Regulation of V-ATPase activity.
Fig. 3: V-ATPases in cancer.
Fig. 4: V-ATPase in cell death and cancer.

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Data availability

The data that support the findings of this study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript.

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Authors and Affiliations

  1. DAMP Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China

    Fangquan Chen & Jiao Liu

  2. Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Rui Kang & Daolin Tang

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  1. Fangquan Chen
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FC and DT wrote the manuscript. RK and JL edited the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.

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Chen, F., Kang, R., Liu, J. et al. The V-ATPases in cancer and cell death. Cancer Gene Ther 29, 1529–1541 (2022). https://doi.org/10.1038/s41417-022-00477-y

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