The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer.
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.
Acquaviva
Jaime
J
Molecular Oncology Research Institute, Tufts University School of Medicine, Tufts Medical Center, Boston, MA 02111, USA.
Wong
Ricky
R
Charest
Al
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D019143:Evolution, Molecular; D048788:Growth and Development / Q000235:genetics*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases