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The P2X7 Receptor in the Maintenance of Cancer Stem Cells, Chemoresistance and Metastasis

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Abstract

Metastasis is the worst prognosis predictor in the clinical course of cancer development. Features of metastatic cancer cells include migratory ability, low degree of differentiation, self-renewal and proliferation potentials, as well as resistance to therapies. Metastatic cells do not present all of the necessary characteristics at once. Indeed, they have a unique phenotypic plasticity, allowing the acquisition of features that make them successful in all steps of metastasis. Cancer stem cells (CSC), the most undifferentiated cells in the tumor mass, display highest metastatic potential and resistance to radio- and chemotherapy. Growing tumors exhibit marked upregulation of P2X7 receptor expression and secrete ATP. Since the P2X7 receptor plays an important role in the maintenance of undifferentiated state of pluripotent cells, its importance on cell fate regulation in the tumor mass is suggested. Considering the extensive crosstalk between CSCs, epithelial-mesenchymal transition, drug resistance and metastasis, current knowledge implicating P2X7 receptor function in these phenomena and new avenues for therapeutic strategies to control metastasis are reviewed.

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Acknowledgments

CL and HU are grateful for the funding of São Paulo Research Foundation, FAPESP (Project No. 2015/19128-2 and 2018/07366-4, respectively), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), Brazil. ILAR is grateful for FAPESP fellowships (Project No. 2017/06132-7-DD). VFAS thanks the National Council for Scientific and Technological Development (CNPq, Project No. 141264/2017-9). Authors have no conflicts of interest to declare.

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  1. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, SP, 05508-900, Brazil

    Vanessa Fernandes Arnaud-Sampaio, Izadora Lorrany Alves Rabelo, Henning Ulrich & Claudiana Lameu

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  1. Vanessa Fernandes Arnaud-Sampaio
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  2. Izadora Lorrany Alves Rabelo
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Correspondence to Claudiana Lameu.

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Arnaud-Sampaio, V.F., Rabelo, I.L.A., Ulrich, H. et al. The P2X7 Receptor in the Maintenance of Cancer Stem Cells, Chemoresistance and Metastasis. Stem Cell Rev and Rep 16, 288–300 (2020). https://doi.org/10.1007/s12015-019-09936-w

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