title: RYK promotes the stemness of glioblastoma cells via the WNT/ β-catenin pathway.
abstract: Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/β-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM cells. Here, we report that Ryk (related-to-receptor tyrosine kinase), an atypical tyrosine kinase receptor, is upregulated in samples from GBM patients as well as in GSCs. Ryk overexpression confers stemness properties to GBM cells through the modulation of the canonical Wnt signaling and by promoting the activation of pluripotency-related transcription factor circuitry and neurosphere formation ability. In contrast, siRNA-mediated knockdown of Ryk expression suppresses this stem-like phenotype. Rescue experiments reveal that stemness-promoting activity of Ryk is attributable, at least in part, to β-catenin stabilization. Furthermore, Ryk overexpression improves cell motility and anchorage independent cell growth. Taken together, our findings demonstrate that Ryk promotes stem cell-like and tumorigenic features to glioma cells its essential for the maintenance of GSCs and could be a target of novel therapies.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Adamo
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fiore
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: De Martino
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.|IEOS, CNR, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Roscigno
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Affinito
authors.affiliation: IRCCS-SDN, Naples, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Donnarumma
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Puoti
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ricci Vitiani
authors.affiliation: Institute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Quintavalle
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.|IEOS, CNR, Naples, Italy.
authors.forename: Gerolama
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D020794:Receptor Protein-Tyrosine Kinases; C118148:Ryk protein, mouse
keywords: glioblastoma; ryk; stem cells; β-catenin