title: GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Tzu-Chi
authors.initials: TC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Syue-Ting
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Huang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: John
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Life Science, Institute of Molecular and Cellular Biology and Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Lang
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Department of Life Science, Institute of Molecular and Cellular Biology and Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ho-Hsiung
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi-Hau
authors.initials: CH
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D014162:Transfection; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D066246:ErbB Receptors; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C512478:EGFR protein, human
keywords: GALNT6; O-glycosylation; epidermal growth factor receptor; invasion; ovarian cancer