P2X7 receptor: a critical regulator and potential target for breast cancer

J Mol Med (Berl). 2021 Mar;99(3):349-358. doi: 10.1007/s00109-021-02041-x. Epub 2021 Jan 23.

Abstract

Breast cancer is currently the most common cancer and the leading cause of cancer death among women worldwide. Advanced breast cancer is prone to metastasis, and there is currently no drug to cure metastatic breast cancer. The purinergic ligand-gated ion channel 7 receptor is an ATP-gated nonselective cation channel receptor and is involved in signal transduction, growth regulation, cytokine secretion, and tumor cell development. Recent studies have shown that upregulation of the P2X7 receptor in breast cancer can mediate AKT signaling pathways, Ca2 þ-activated SK3 potassium channels, and EMT and regulate the secretion of small extracellular vesicles to promote breast cancer invasion and migration, which are affected by factors such as hypoxia and ATP. In addition, studies have shown that microRNAs can bind to the 3' untranslated region of the P2X7 receptor, which affects the occurrence and development of breast cancer by upregulating and downregulating P2X7 receptor expression. Studies have shown that new P2X7 receptor inhibitors, such as emodin and Uncaria tomentosa, can inhibit P2X7 receptor-mediated breast cancer invasion and are expected to be used clinically. This article reviews the research progress on the relationship between the P2X7 receptor and breast cancer to provide new ideas and a basis for clinical diagnosis and treatment.

Keywords: ATP; Breast cancer; P2X7 receptor; P2X7 receptor antagonist.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Cat's Claw
  • Cations / metabolism
  • Disease Progression
  • Emodin / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ion Transport
  • Molecular Targeted Therapy / methods*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / physiology*
  • Plant Extracts / therapeutic use
  • Purinergic P2X Receptor Antagonists / pharmacology
  • Purinergic P2X Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2X7 / chemistry
  • Receptors, Purinergic P2X7 / drug effects
  • Receptors, Purinergic P2X7 / physiology*
  • Signal Transduction / physiology
  • Structure-Activity Relationship
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • Cations
  • Neoplasm Proteins
  • P2RX7 protein, human
  • Plant Extracts
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate
  • cat's claw extract
  • Emodin