title: Antiangiogenic VEGF-Ax: A New Participant in Tumor Angiogenesis.
abstract: The transcript of the angiogenic factor vascular endothelial growth factor A (VEGF-A) is subject to a multitude of stimulus-dependent, posttranscriptional regulatory events, consistent with its unusually long 3' untranslated region. We have recently reported translational readthrough of VEGFA mRNA whereby translating ribosomes traverse the canonical stop codon to a conserved, downstream stop codon, generating VEGF-Ax ("x" for extended), a novel, extended isoform with an additional 22 amino acids appended at the C-terminus. This event is the first vertebrate example of protein-regulated, programmed translational readthrough that generates a protein with a known function. Remarkably, VEGF-Ax exhibits potent antiangiogenic activity, both in vitro and in vivo, thus raising profound clinical implications, particularly with respect to cancer treatment. In this review, we discuss the potential of VEGF-Ax as a therapeutic agent and drug target, as well as its possible role in the failure of, or resistance to, conventional anti-VEGF therapies in many types of cancers.
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. Department of Biochemistry, Indian Institute of Science, Bangalore, India.
authors.forename: Sandeepa M
authors.initials: SM
authors.lastname: Eswarappa
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. foxp@ccf.org.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Fox
mesh_terms: D020533:Angiogenesis Inhibitors / Q000502:physiology*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000502:physiology; D020543:Proteome / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014714:Vertebrates / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D020033:Protein Isoforms; D020543:Proteome; D042461:Vascular Endothelial Growth Factor A