GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity
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Tzu-Chi Lin1,*, Syue-Ting Chen2,*, Min-Chuan Huang2, John Huang3, Chia-Lang Hsu4, Hsueh-Fen Juan4, Ho-Hsiung Lin1 and Chi-Hau Chen1
1Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
2Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan
3Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
4Department of Life Science, Institute of Molecular and Cellular Biology and Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
*These authors have contributed equally to this work
Chi-Hau Chen, email: email@example.com
Keywords: ovarian cancer, GALNT6, epidermal growth factor receptor, O-glycosylation, invasion
Received: September 24, 2016 Accepted: March 13, 2017 Published: March 28, 2017
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.
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