Phospholipase D as a key modulator of cancer progression

Biol Rev Camb Philos Soc. 2020 Aug;95(4):911-935. doi: 10.1111/brv.12592. Epub 2020 Feb 19.

Abstract

The phospholipase D (PLD) family has a ubiquitous expression in cells. PLD isoforms (PLDs) and their hydrolysate phosphatidic acid (PA) have been demonstrated to engage in multiple stages of cancer progression. Aberrant expression of PLDs, especially PLD1 and PLD2, has been detected in various cancers. Inhibition or elimination of PLDs activity has been shown to reduce tumour growth and metastasis. PLDs and PA also serve as downstream effectors of various cell-surface receptors, to trigger and regulate propagation of intracellular signals in the process of tumourigenesis and metastasis. Here, we discuss recent advances in understanding the functions of PLDs and PA in discrete stages of cancer progression, including cancer cell growth, invasion and migration, and angiogenesis, with special emphasis on the tumour-associated signalling pathways mediated by PLDs and PA and the functional importance of PLDs and PA in cancer therapy.

Keywords: angiogenesis; cancer; metastasis; phosphatidic acid; phospholipase D; signalling transduction; tumourigenesis.

Publication types

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

MeSH terms

  • Angiogenesis Inducing Agents
  • Animals
  • Cell Movement / physiology
  • Disease Progression
  • Epithelial-Mesenchymal Transition / physiology
  • Humans
  • Mice
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Metastasis / prevention & control
  • Neoplasms / enzymology*
  • Neoplasms / pathology*
  • Neoplasms / prevention & control
  • Phosphatidic Acids / metabolism
  • Phospholipase D / metabolism*
  • Receptors, Growth Factor / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Phosphatidic Acids
  • Receptors, Growth Factor
  • Phospholipase D