https://scholars.lib.ntu.edu.tw/handle/123456789/452900
標題: | GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity | 作者: | Lin, Tzu-Chi Chen, Syue-Ting MIN-CHUAN HUANG JOHN HUANG CHIA-LANG HSU HSUEH-FEN JUAN HO-HSIUNG LIN CHI-HAU CHEN |
公開日期: | 2017 | 卷: | 8 | 期: | 26 | 起(迄)頁: | 42588-42601 | 來源出版物: | Oncotarget | 摘要: | Ovarian cancer is the most lethal of the gynecologic malignancies. N-acetylgalactosaminyltransferase 6 (GALNT6), an enzyme that mediates the initial step of mucin type-O glycosylation, has been reported to regulate mammary carcinogenesis. However, the expression and role of GALNT6 in ovarian cancer are still unclear. Here we showed that high GALNT6 expression correlates with increased recurrence, lymph node metastasis, and chemoresistance in ovarian endometrioid and clear cell carcinomas; and higher GALNT6 levels are significantly associated with poorer patient survivals. GALNT6 knockdown with two independent siRNAs significantly suppressed viability, migration, and invasion of ovarian cancer cells. Using phospho-RTK array and Western blot analyses, we identified EGFR as a critical target of GALNT6. GALNT6 knockdown decreased phosphorylation of EGFR, whereas GALNT6 overexpression increased the phosphorylation. Lectin pull-down assays with Vicia villosa agglutinin (VVA) indicated that GALNT6 was able to modify O-glycans on EGFR. Moreover, the GALNT6-enhanced invasive behavior was significantly reversed by erlotinib, an EGFR inhibitor. Our results suggest that GALNT6 expression is associated with poor prognosis of ovarian cancer and enhances the aggressive behavior of ovarian cancer cells by regulating EGFR activity. © Lin et al. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/452900 | DOI: | 10.18632/oncotarget.16585 |
顯示於: | 醫學系 |
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