title: GALNT2 suppresses malignant phenotypes through IGF-1 receptor and predicts favorable prognosis in neuroblastoma.
abstract: Aberrant expression of the simple mucin-type carbohydrate antigens such as Tn antigen is associated with malignant transformation and cancer progression. N-acetylgalactosaminyltransferase 2 (GALNT2), one of the enzymes that mediate the initial step of mucin-type O-glycosylation, is responsible for forming Tn antigen. GALNT2 is expressed differentially in nervous tissues during mouse embryogenesis; however, the role of GALNT2 in neuroblastoma (NB) remains unclear. Here we showed that increased GALNT2 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as younger age at diagnosis, early clinical stage, primary tumor originated from the extra-adrenal site, favorable INPC histology, and MYCN non-amplification. Multivariate analysis showed that GALNT2 expression is an independent prognostic factor for better survival for NB patients. GALNT2 overexpression suppressed IGF-1-induced cell growth, migration, and invasion of NB cells, whereas GALNT2 knockdown enhanced these NB phenotypes. Mechanistic investigations demonstrated that GALNT2 overexpression modified O-glycans on IGF-1R, which suppressed IGF-1-triggered IGF-1R dimerization and subsequent downstream signaling events. Conversely, these properties were reversed by GALNT2 knockdown in NB cells. Our findings suggest that GALNT2 regulates malignant phenotypes of NB cells through the IGF-1R signaling pathway, suggesting a critical role for GALNT2 in the pathogenesis of NB.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Ho
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Meng-Yao
authors.initials: MY
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yung-Li
authors.initials: YL
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shiann-Tarng
authors.initials: ST
authors.lastname: Jou
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Dong-Tsamn
authors.initials: DT
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsiu-Hao
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan. Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Huang
mesh_terms: D000818:Animals; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D009447:Neuroblastoma / Q000401:mortality / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D017350:N-Acetylgalactosaminyltransferases; D017526:Receptor, IGF Type 1; D000097763:Polypeptide N-acetylgalactosaminyltransferase