α2,3-sialyltransferase type I regulates migration and peritoneal dissemination of ovarian cancer cells
| Autor: | Pi-Lin Sung, Shie-Liang Hsieh, Peng-Hui Wang, Kuo Chang Wen, Oscar K. Lee, Yu-Ting Chou, Cheng-Wen Wu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
epithelial ovarian cancer
0301 basic medicine Gerontology soyasaponin I endocrine system diseases Kaplan-Meier Estimate Carcinoma Ovarian Epithelial Mice 0302 clinical medicine Cell Movement Antineoplastic Combined Chemotherapy Protocols Medicine Neoplasms Glandular and Epithelial Epidermal growth factor receptor Peritoneal Neoplasms EGFR inhibitors Ovarian Neoplasms biology Drug Synergism Cell migration Prognosis Immunohistochemistry female genital diseases and pregnancy complications ErbB Receptors Survival Rate medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Female Peritoneum Signal transduction Signal Transduction Research Paper beta-Galactoside alpha-2 3-Sialyltransferase Antineoplastic Agents Ovary 03 medical and health sciences In vivo Cell Line Tumor Biomarkers Tumor Animals Humans Immunoprecipitation Neoplasm Invasiveness Oleanolic Acid Protein Kinase Inhibitors Neoplasm Staging business.industry Saponins Microarray Analysis medicine.disease Sialyltransferases Mice Inbred C57BL 030104 developmental biology α2 3-sialyltransferases type I Cancer research biology.protein epidermal growth factor receptor business Ovarian cancer |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.15994 |
| Popis: | Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic cancers due to advanced stage presentation, peritoneal dissemination, and refractory ascites at diagnosis. We investigated the role of α2,3-sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and human EOC tissue arrays. We found that high expression of ST3GalI was associated with advanced stage EOC. Transwell migration and cell invasion assays showed that high ST3GalI expression enhanced migration of EOC cells. We also observed that there was a linear relation between ST3GalI expression and epidermal growth factor receptor (EGFR) signaling in EOC patients, and that high ST3GalI expression blocked the effect of EGFR inhibitors. Co-Immunoprecipitation experiments demonstrated that ST3GalI and EGFR were present in the same protein complex. Inhibition of ST3GalI using a competitive inhibitor, Soyasaponin I (SsaI), inhibited tumor cell migration and dissemination in the in vivo mouse model with transplanted MOSEC cells. Further, SsaI synergistically enhanced the anti-tumor effects of EGFR inhibitor on EOC cells. Our study demonstrates that ST3GalI regulates ovarian cancer cell migration and peritoneal dissemination via EGFR signaling. This suggests α2,3-linked sialylation inhibitors in combination with EGFR inhibitors could be effective agents for the treatment of EOC. |
| Databáze: | OpenAIRE |
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