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Autocrine and paracrine purinergic signaling in the most lethal types of cancer

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Abstract

Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor formation and propagation to other tissues, causing tissue and organ malfunction and death. Despite the undeniable improvement in cancer diagnostics and therapy, there is an urgent need for new therapeutic and preventive strategies with improved efficacy and fewer side effects. In this context, purinergic signaling emerges as an interesting candidate as a cancer biomarker or therapeutic target. There is abundant evidence that tumor cells have significant changes in the expression of purinergic receptors, which comprise the G-protein coupled P2Y and AdoR families of receptors and the ligand-gated ion channel P2X receptors. Tumor cells also exhibit changes in the expression of nucleotidases and other enzymes involved in nucleotide metabolism, and the concentrations of extracellular nucleotides are significantly higher than those observed in normal cells. In this review, we will focus on the potential role of purinergic signaling in the ten most lethal cancers (lung, breast, colorectal, liver, stomach, prostate, cervical, esophagus, pancreas, and ovary), which together are responsible for more than 5 million annual deaths.

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Acknowledgements

This work was funded by grants from Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica-UNAM (PAPIIT-UNAM) #IN202620 to F.G.V.-C., #IN202121 to M.D.-M.; Consejo Nacional de Ciencia y Tercnología (CONACYT-México) #284-557 to M.D.M.; Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT-Chile) Regular Grant # 1161490, FONDEQUIP-Chile EQM140100; and Millennium Nucleus for the Study of Pain (MiNuSPain) to C.C. MiNuSPain is a Millennium Nucleus supported by the Millennium Science Initiative of the Ministry of Science, Technology, Knowledge and Innovation (Chile). We are grateful to Jessica González Norris for proofreading and to Biol. Jazmín Vázquez-Méndez for the art in Fig. 1.

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PAPIIT-UNAM #IN202620 and #IN202121; CONACYT#284-557; FONDECYT# 1161490, FONDEQUIP EQM140100 and MiNuSPain, MiNuSPain is a Millennium Nucleus supported by the Millennium Science Initiative of the Ministry of Science, Technology, Knowledge and Innovation (Chile).

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  1. Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile

    M. Reyna-Jeldes, J. A. Madariaga & C. Coddou

  2. Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile

    M. Reyna-Jeldes & C. Coddou

  3. Núcleo para el Estudio del Cáncer a nivel Básico, Aplicado y Clínico, Universidad Católica del Norte, Antofagasta, Chile

    M. Reyna-Jeldes, J. A. Madariaga & C. Coddou

  4. Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Querétaro, México

    M. Díaz-Muñoz & F. G. Vázquez-Cuevas

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  1. M. Reyna-Jeldes
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  2. M. Díaz-Muñoz
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  4. C. Coddou
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  5. F. G. Vázquez-Cuevas
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C.C. and F.G. V. C, conceived the paper. All the authors wrote and reviewed the paper.

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Reyna-Jeldes, M., Díaz-Muñoz, M., Madariaga, J.A. et al. Autocrine and paracrine purinergic signaling in the most lethal types of cancer. Purinergic Signalling 17, 345–370 (2021). https://doi.org/10.1007/s11302-021-09785-8

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