Clinical significance of P‑class pumps in cancer (Review)

Themistocleous,Sophia C.; Yiallouris,Andreas; Tsioutis,Constantinos; Zaravinos,Apostolos; Johnson,Elizabeth O.; Patrikios,Ioannis

doi:10.3892/ol.2021.12919

Clinical significance of P‑class pumps in cancer (Review)

Authors:
- Sophia C. Themistocleous
- Andreas Yiallouris
- Constantinos Tsioutis
- Apostolos Zaravinos
- Elizabeth O. Johnson
- Ioannis Patrikios
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Affiliations: Department of Medicine, School of Medicine, European University Cyprus, 2404 Nicosia, Cyprus, Department of Life Sciences, School of Sciences, European University Cyprus, 2404 Nicosia, Cyprus
Published online on: July 12, 2021 https://doi.org/10.3892/ol.2021.12919
Article Number: 658
Copyright: © Themistocleous et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

P‑class pumps are specific ion transporters involved in maintaining intracellular/extracellular ion homeostasis, gene transcription, and cell proliferation and migration in all eukaryotic cells. The present review aimed to evaluate the role of P‑type pumps [Na⁺/K⁺ ATPase (NKA), H⁺/K⁺ ATPase (HKA) and Ca2⁺‑ATPase] in cancer cells across three fronts, namely structure, function and genetic expression. It has been shown that administration of specific P‑class pumps inhibitors can have different effects by: i) Altering pump function; ii) inhibiting cell proliferation; iii) inducing apoptosis; iv) modifying metabolic pathways; and v) induce sensitivity to chemotherapy and lead to antitumor effects. For example, the NKA β2 subunit can be downregulated by gemcitabine, resulting in increased apoptosis of cancer cells. The sarcoendoplasmic reticulum calcium ATPase can be inhibited by thapsigargin resulting in decreased prostate tumor volume, whereas the HKA α subunit can be affected by proton pump inhibitors in gastric cancer cell lines, inducing apoptosis. In conclusion, the present review highlighted the central role of P‑class pumps and their possible use and role as anticancer cellular targets for novel therapeutic chemical agents.

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