|Title:||GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity||Authors:||Lin, Tzu-Chi
Hsu, Chia Lang
|Keywords:||GALNT6; O-glycosylation; epidermal growth factor receptor; invasion; ovarian cancer||Issue Date:||2017||Publisher:||Impact Journals, LLC||Journal Volume:||8||Journal Issue:||26||Start page/Pages:||42588-42601||Source:||Oncotarget||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.
epidermal growth factor receptor; erlotinib; n acetylgalactosaminyltransferase; n acetylgalactosaminyltransferase 6; unclassified drug; adult; Article; cancer prognosis; cancer resistance; cell invasion; cell migration; cell viability; clear cell carcinoma; controlled study; disease free survival; endometrioid carcinoma; female; gene expression; human; human tissue; lymph node metastasis; major clinical study; ovarian cancer cell line; ovary carcinoma; overall survival; protein glycosylation; protein phosphorylation; tumor invasion; tumor recurrence
|Appears in Collections:||腫瘤醫學研究所|
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