Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives

Biochim Biophys Acta. 2015 Oct;1848(10 Pt B):2584-602. doi: 10.1016/j.bbamem.2014.10.029. Epub 2014 Nov 14.

Abstract

P2X7 is an intriguing ionotropic receptor for which the activation by extracellular ATP induces rapid inward cationic currents and intracellular signalling pathways associated with numerous physiological processes such as the induction of the inflammatory cascade, the survival and proliferation of cells. In contrast, long-term stimulation of P2X7 is generally associated with membrane permeabilisation and cell death. Recently, P2X7 has attracted great attention in the cancer field, and particularly in the neoplastic transformation and the progression of solid tumours. A growing number of studies were published; however they often appeared contradictory in their results and conclusions. As such, the involvement of P2X7 in the oncogenic process remains unclear so far. The present review aims to discuss the current knowledge and hypotheses on the involvement of the P2X7 receptor in the development and progression of solid tumours, and highlight the different aspects that require further clarification in order to decipher whether P2X7 could be considered as a cancer biomarker or as a target for pharmacological intervention. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

Keywords: Biomarker; Cancer; Extracellular ATP; P2X7; Pharmacological target.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / therapeutic use*
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Purinergic P2X Receptor Antagonists / chemical synthesis
  • Purinergic P2X Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2X7 / genetics*
  • Receptors, Purinergic P2X7 / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • P2RX7 protein, human
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate