title: Splice Variants of the RTK Family: Their Role in Tumour Progression and Response to Targeted Therapy.
abstract: Receptor tyrosine kinases (RTKs) belong to a family of transmembrane receptors that display tyrosine kinase activity and trigger the activation of downstream signalling pathways mainly involved in cell proliferation and survival. RTK amplification or somatic mutations leading to their constitutive activation and oncogenic properties have been reported in various tumour types. Numerous RTK-targeted therapies have been developed to counteract this hyperactivation. Alternative splicing of pre-mRNA has recently emerged as an important contributor to cancer development and tumour maintenance. Interestingly, RTKs are alternatively spliced. However, the biological functions of RTK splice variants, as well as the upstream signals that control their expression in tumours, remain to be understood. More importantly, it remains to be determined whether, and how, these splicing events may affect the response of tumour cells to RTK-targeted therapies, and inversely, whether these therapies may impact these splicing events. In this review, we will discuss the role of alternative splicing of RTKs in tumour progression and response to therapies, with a special focus on two major RTKs that control proliferation, survival, and angiogenesis, namely, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-1 (VEGFR1).
authors.affiliation: Team RNA Splicing, Cell Signaling and Response to Therapies, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble 38702, France. cherineaf@gmail.com.
authors.forename: Cherine
authors.initials: C
authors.lastname: Abou-Fayçal
authors.affiliation: Team RNA Splicing, Cell Signaling and Response to Therapies, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble 38702, France. anne-sophie.hatat@univ-grenoble-alpes.fr.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Hatat
authors.affiliation: Team RNA Splicing, Cell Signaling and Response to Therapies, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble 38702, France. sylvie.gazzeri@univ-grenoble-alpes.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gazzeri
authors.affiliation: Team RNA Splicing, Cell Signaling and Response to Therapies, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble 38702, France. beatrice.eymin@univ-grenoble-alpes.fr.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Eymin
mesh_terms: D017398:Alternative Splicing; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D018450:Disease Progression; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D005810:Multigene Family; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012322:RNA Precursors / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D012322:RNA Precursors; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: EGFR; VEGFR; alternative splicing; angiogenesis; cancer; receptor tyrosine kinases; targeted therapies; tumourigenesis