https://scholars.lib.ntu.edu.tw/handle/123456789/615981
標題: | C1GALT1 expression predicts a favorable prognosis and suppresses malignant phenotypes via TrkA signaling in neuroblastoma | 作者: | NENG-YU LIN Chen, Syue-Ting Chang, Hsiu-Ling MENG-YAO LU YUNG-LI YANG SHU-WEI CHOU Lin, Dong-Tsamn Lin, Kai-Hsin SHIANN-TANG JOU WEN-MING HSU MIN-CHUAN HUANG HSIU-HAO CHANG |
關鍵字: | IN-SITU HYBRIDIZATION; N-MYC AMPLIFICATION; O-GLYCOSYLATION; CANCER; THROMBOCYTOPENIA; CLASSIFICATION; PROMOTES; DISEASE; FAMILY; GROWTH | 公開日期: | 15-二月-2022 | 出版社: | SPRINGERNATURE | 卷: | 11 | 期: | 1 | 來源出版物: | Oncogenesis | 摘要: | Neuroblastoma (NB) is a childhood tumor derived from the sympathoadrenal lineage of the neural crest progenitor cells. Core 1 β1,3-galactosyltransferase (C1GALT1) controls the crucial step of GalNAc-type O-glycosylation, and its altered expression affects cancer behaviors. However, the role of C1GALT1 in NB tumors remains unclear. Our data showed that C1GALT1 expression was significantly associated with differentiated tumor histology, correlated with TrkA expression, and predicted good prognosis independently in NB. Downregulation of C1GALT1 promotes malignant behaviors of NB cells in vitro and in vivo. Mechanistic investigation showed that knockdown of C1GALT1 in NB cells increased TrkA pulled down through Vicia villosa agglutinin beads, indicating the modulation of O-glycans on TrkA by C1GALT1, and silencing C1GALT1 suppressed the TrkA expression on the NB cell surface. Overexpression of C1GALT1 increased the protein levels of TrkA and promoted the differentiation of NB cells, whereas knockdown of TrkA inhibited C1GALT1-induced neuronal differentiation. Moreover, the inhibitory effects of migration and invasion in C1GALT1-overexpressing NB cells were blocked by TrkA downregulation. C1GALT1 knockdown enhanced AKT phosphorylation but attenuated ERK phosphorylation, and these properties were consistent in C1GALT1-overexpressing NB cells with TrkA knockdown. Taken together, our data provided the first evidence for the existence of GalNAc-type O-glycans on TrkA and altered O-glycan structures by C1GALT1 can regulate TrkA signaling in NB cells. This study sheds light on the novel prognostic role of C1GALT1 in NB and provides new information of C1GALT1 and TrkA on the pathogenesis of NB. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/615981 | ISSN: | 2157-9024 | DOI: | 10.1038/s41389-022-00383-w |
顯示於: | 解剖學暨細胞生物學科所 |
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