α2,3-sialyltransferase type I regulates migration and peritoneal dissemination of ovarian cancer cells

Kuo Chang Wen, Pi Lin Sung, Shie Liang Hsieh, Yu Ting Chou, Oscar Kuang Sheng Lee, Cheng-Wen Wu Lee, Peng Hui Wang*

*此作品的通信作者

研究成果: Article同行評審

33 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)29013-29027
頁數15
期刊Oncotarget
8
發行號17
DOIs
出版狀態Published - 1 一月 2017

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