https://scholars.lib.ntu.edu.tw/handle/123456789/457879
標題: | Mucin glycosylating enzyme GALNT2 regulates the malignant character of hepatocellular carcinoma by modifying the EGF receptor | 作者: | YAO-MING WU Liu C.-H. REY-HENG HU Huang M.-J. Lee Jr. J. CHI-HAU CHEN JOHN HUANG HONG-SHIEE LAI PO-HUANG LEE WEN-MING HSU Huang H.-C. MIN-CHUAN HUANG |
公開日期: | 2011 | 卷: | 71 | 期: | 23 | 起(迄)頁: | 7270-7279 | 來源出版物: | Cancer Research | 摘要: | Extracellular glycosylation is a critical determinant of malignant character. Here, we report that N-acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that mediates the initial step of mucin type-O glycosylation, is a critical mediator of malignant character in hepatocellular carcinoma (HCC) that acts by modifying the activity of the epidermal growth factor receptor (EGFR). GALNT2 mRNA and protein were downregulated frequently in HCC tumors where these events were associated with vascular invasion and recurrence. Restoring GALNT2 expression in HCC cells suppressed EGF-induced cell growth, migration, and invasion in vitro and in vivo. Mechanistic investigations revealed that the status of the O-glycans attached to the EGFR was altered by GALNT2, changing EGFR responses after EGF binding. Inhibiting EGFR activity with erlotinib decreased the malignant characters caused by siRNA-mediated knockdown of GALNT2 in HCC cells, establishing the critical role of EGFR in mediating the effects of GALNT2 expression. Taken together, our results suggest that GALNT2 dysregulation contributes to the malignant behavior of HCC cells, and they provide novel insights into the significance of O-glycosylation in EGFR activity and HCC pathogenesis. ?2011 AACR. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-82655161263&doi=10.1158%2f0008-5472.CAN-11-1161&partnerID=40&md5=126cceb27229473d91a88060ee352263 https://scholars.lib.ntu.edu.tw/handle/123456789/457879 |
ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-11-1161 | SDG/關鍵字: | epidermal growth factor receptor; erlotinib; messenger RNA; mucin; n acetylgalactosaminyltransferase; protein GALNT2; small interfering RNA; unclassified drug; animal experiment; animal model; article; cancer inhibition; cancer invasion; cancer recurrence; cell growth; cell invasion; cell migration; controlled study; down regulation; drug protein binding; enzyme activity; enzyme glycosylation; female; human; human cell; human tissue; in vitro study; in vivo study; liver cell carcinoma; mouse; nonhuman; nucleotide sequence; priority journal; protein binding; protein modification; protein synthesis inhibition; regulatory mechanism; Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Epidermal Growth Factor; Female; Gene Knockdown Techniques; Glycosylation; Hep G2 Cells; Humans; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Mucins; N-Acetylgalactosaminyltransferases; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Quinazolines; Receptor, Epidermal Growth Factor; RNA, Messenger |
顯示於: | 醫學系 |
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