title: SOX9-mediated upregulation of LGR5 is important for glioblastoma tumorigenicity.
abstract: LGR5 plays an important role in the self-renewal of stem cells and is used as a marker identifying self-renewing stem cells in small intestine and hair follicles. Moreover, LGR5 has been reported to be overexpressed in several cancers. SOX9 is a transcription factor that plays a key role in development, differentiation and lineage commitment in various tissues. It has also been reported that SOX9 is overexpressed in a variety of cancers and contributes to their malignant phenotype. Here we show that LGR5 is required for the tumorigenicity of glioblastoma cells. We further show that SOX9 is upregulated in glioblastoma cells and directly enhances the expression of LGR5. We also demonstrate that knockdown of SOX9 suppresses the proliferation and tumorigenicity of glioblastoma cells. These results suggest that SOX9-mediated transcriptional regulation of LGR5 is critical for the tumorigenicity of glioblastoma cells. We speculate that the SOX9-LGR5 pathway could be a potentially promising target for the therapy of glioblastoma.
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hiraoka
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Kaneko
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nasu-Nishimura
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Koyama-Nasu
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address: akiyama@iam.u-tokyo.ac.jp.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human
keywords: Glioblastoma; Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5); Sry-related high-mobility group (HMG) box 9 (SOX9); Tumorigenicity