Role of G12 proteins in oncogenesis and metastasis

Br J Pharmacol. 2009 Sep;158(1):32-40. doi: 10.1111/j.1476-5381.2009.00180.x. Epub 2009 Apr 30.

Abstract

The G12 subfamily of heterotrimeric guanine nucleotide-binding proteins consists of two alpha subunits, G alpha12 and G alpha13. These proteins mediate signalling via G protein-coupled receptors and have been implicated in various physiological and pathophysiological processes. A number of direct and indirect effectors of G alpha12 and G alpha13 have been identified that mediate, or have been proposed to mediate, the diverse cellular responses accompanying activation of G12 proteins. This review describes the signalling pathways and cellular events stimulated by G12 proteins, with a particular emphasis on processes that are important in regulating cell migration and invasion, and could potentially be involved in the pathophysiology of cancer metastasis. Experimental findings directly implicating G12 proteins in the spread of metastatic disease are also summarized, indicating the importance of targeted inhibition of G12 signalling as a potential therapeutic option for locally advanced and metastatic disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Movement / physiology
  • Drug Delivery Systems
  • GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
  • GTP-Binding Protein alpha Subunits, G12-G13 / physiology*
  • Humans
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Invasiveness / physiopathology
  • Neoplasm Invasiveness / prevention & control
  • Neoplasms / chemistry
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplasms / physiopathology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • GTP-Binding Protein alpha Subunits, G12-G13