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

Purinergic Signal. 2021 Sep;17(3):345-370. doi: 10.1007/s11302-021-09785-8. Epub 2021 May 12.

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.

Keywords: ATP; Adenosine; Breast cancer; Cervicouterine cancer; Colorectum cancer; Ectonucleotidases; Esophagous cancer; Gastric cancer; Hepatocellular cancer; Lung cancer; Ovarian cancer; Pancreas cancer; Prostate cancer; Purinergic receptors; UDP; UTP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Autocrine Communication / physiology*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / mortality
  • Paracrine Communication / physiology*
  • Receptors, Purinergic / genetics
  • Receptors, Purinergic / metabolism*
  • Signal Transduction / physiology

Substances

  • Receptors, Purinergic
  • Adenosine Triphosphate