發育再生研究快報 2014/10/23 GALNT2 suppresses malignant phenotypes through IGF-1 receptor and predicts favorable prognosis in neuroblastoma Wan-Ling Ho1,4,6,7,#(何宛玲),Chih-Hsing Chou5,#(周志行), Yung-Ming Jeng2, Meng-Yao Lu1, Yung-Li Yang1, Shiann-Tarng Jou1, Dong-Tsamn Lin1, Hsiu-Hao Chang1,*, Kai-Hsin Lin1, Wen-Ming Hsu3,8,*(許文明), Min-Chuan Huang5,8,* (黃敏銓) Departments of 1Pediatrics, 2Pathology, and 3Surgery, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institutes of 4Clinical Medicine and 5 Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan 7School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 8Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan Oncotarget. (IF: 6.627, Oncology: 17/202) 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.
Posted on: Thu, 23 Oct 2014 01:58:58 +0000
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