title: KLRC3, a Natural Killer receptor gene, is a key factor involved in glioblastoma tumourigenesis and aggressiveness.
abstract: Glioblastoma is the most lethal brain tumour with a poor prognosis. Cancer stem cells (CSC) were proposed to be the most aggressive cells allowing brain tumour recurrence and aggressiveness. Current challenge is to determine CSC signature to characterize these cells and to develop new therapeutics. In a previous work, we achieved a screening of glycosylation-related genes to characterize specific genes involved in CSC maintenance. Three genes named CHI3L1, KLRC3 and PRUNE2 were found overexpressed in glioblastoma undifferentiated cells (related to CSC) compared to the differentiated ones. The comparison of their roles suggest that KLRC3 gene coding for NKG2E, a protein initially identified in NK cells, is more important than both two other genes in glioblastomas aggressiveness. Indeed, KLRC3 silencing decreased self-renewal capacity, invasion, proliferation, radioresistance and tumourigenicity of U87-MG glioblastoma cell line. For the first time we report that KLRC3 gene expression is linked to glioblastoma aggressiveness and could be a new potential therapeutic target to attenuate glioblastoma.
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Cheray
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bessette
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lacroix
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Mélin
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Soha
authors.initials: S
authors.lastname: Jawhari
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinet
authors.affiliation: Oncology Department, University Hospital, Limoges, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Deluche
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.|Oncology Department, University Hospital, Limoges, France.|Immunology Lab., University Hospital, Limoges, France.|Radiotherapy Department, University Hospital, Limoges, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Clavère
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.|Oncology Department, University Hospital, Limoges, France.|Immunology Lab., University Hospital, Limoges, France.|Radiotherapy Department, University Hospital, Limoges, France.|Pathology and Anatomy, CBRS, Limoges, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Durand
authors.affiliation: Laboratorio de Oncología Molecular, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha/PCyTA/Unidad de Biomédicina UCLM-CSIC, Albacete, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sanchez-Prieto
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.|Immunology Lab., University Hospital, Limoges, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Jauberteau
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Battu
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies, Faculty of Medicine of Limoges, University of Limoges, Limoges, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lalloué
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002999:Clone Cells; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008819:Mice, Nude; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000378:metabolism; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527062:KLRC3 protein, human; D008565:Membrane Proteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D034741:RNA, Small Interfering; C110546:TYROBP protein, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: NKG2E/KLRC3; biomarker; glioblastoma; tumourigenicity