The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer

Biochim Biophys Acta. 2009 Jan;1795(1):37-52. doi: 10.1016/j.bbcan.2008.07.006. Epub 2008 Aug 3.

Abstract

The proto-oncogene receptor tyrosine kinase ROS was originally discovered through the identification of oncogenic variants isolated from tumors. These discoveries spearheaded a body of work aimed at elucidating the function of this evolutionarily conserved receptor in development and cancer. Through genetic and biochemical approaches, progress in the characterization of ROS points to distinctive roles in the program of epithelial cell differentiation during the development of a variety of organs. Although substantial, these advances remain hampered by the absence of an identified ligand, making ROS one of the last two remaining orphan receptor tyrosine kinases. Recent studies on the oncogenic activation of ROS as a result of different chromosomal rearrangements found in brain and lung cancers have shed light on the molecular mechanisms underlying ROS transforming activities. ROS and its oncogenic variants therefore constitute clinically relevant targets for cancer therapeutic intervention. This review highlights the various roles that this receptor plays in multiple system networks in normalcy and disease and points to future directions towards the elucidation of ROS function in the context of ligand identification, signaling pathways and clinical applications.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Cell Survival / genetics
  • Evolution, Molecular
  • Growth and Development / genetics*
  • Humans
  • Mice
  • Models, Biological
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Protein-Tyrosine Kinases / physiology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology

Substances

  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases