title: Ryk is essential for Wnt-5a-dependent invasiveness in human glioma.
abstract: Glioblastoma is characterized by marked invasiveness, but little is known about the mechanism of invasion in glioblastoma cells. Wnts are secreted ligands that regulate cell proliferation, differentiation, motility and fate at various developmental stages. In adults, misregulation of the Wnt pathway is associated with several diseases. Recently, we reported that Wnt-5a was overexpressed and correlated with cell motility and infiltrative activity through the regulation of matrix metalloproteinase (MMP)-2 in glioma-derived cells. Although several receptors for Wnt-5a were identified, the receptors of Wnt-5a that mediate cellular responses of glioma were not clearly identified. Knockdown of receptor-like tyrosine kinase (Ryk) but not that of Ror2 suppressed the activity of MMP-2 and Wnt-5a-dependent invasive activity in glioma cells. These results suggest that Ryk is important for the Wnt-5a-dependent induction of MMP-2 and invasive activity in glioma-derived cells and that Ryk might have a novel patho-physiological function in adult cancer invasion. Furthermore, not only the expression of Wnt-5a but also that of Frizzled (Fz)-2 and Ryk was correlated with the WHO histological grade in 38 human glioma tissues. Taking these findings together, Fz-2 and Ryk could be therapeutic or pharmacological target molecules for the control of Wnt-5a-dependent invasion of human glioma in the near future.
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDepartment of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Habu
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Koyama
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kishida
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDepartment of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kamino
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Iijima
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDepartment of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fuchigami
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokimura
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDepartment of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tokudome
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Chihaya
authors.initials: C
authors.lastname: Koriyama
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hirano
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.affiliation: Department of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDepartment of Biochemistry and Genetics; Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences; Department of Pharmacy, Kagoshima Prefectural Satunan Hospital; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences; Natural Science Centre for Research and Education, Kagoshima University; and Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan shosei@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Shosei
authors.initials: S
authors.lastname: Kishida
mesh_terms: D002460:Cell Line; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C080836:RYK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2
keywords: MMP-2; Ryk; Wnt-5a signal; glioma; invasion