title: MET signaling regulates glioblastoma stem cells.
abstract: Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM. Here, we identified a distinct fraction of cells expressing a high level of MET in human primary GBM specimens that were preferentially localized in perivascular regions of human GBM biopsy tissues and were found to be highly clonogenic, tumorigenic, and resistant to radiation. Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs. Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target.
authors.affiliation: Cancer Stem Cell Research Center, Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.forename: Juyoun
authors.initials: J
authors.lastname: Jin
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kim
authors.forename: Kang
authors.initials: K
authors.lastname: Ho Kim
authors.forename: Yonghyun
authors.initials: Y
authors.lastname: Kim
authors.forename: Bong
authors.initials: B
authors.lastname: Gu Kang
authors.forename: Youn-Jung
authors.initials: YJ
authors.lastname: Kang
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Cheong
authors.forename: Paul H
authors.initials: PH
authors.lastname: Song
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
authors.forename: Ho Jun
authors.initials: HJ
authors.lastname: Seol
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kong
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: Jeongwu
authors.initials: J
authors.lastname: Lee
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D034741:RNA, Small Interfering; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met