Oncotarget

Research Papers:

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 and Peng-Hui Wang _

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Oncotarget. 2017; 8:29013-29027. https://doi.org/10.18632/oncotarget.15994

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Abstract

Kuo-Chang Wen1,2,3, Pi-Lin Sung1,2,3, Shie-Liang Hsieh2,4, Yu-Ting Chou5, Oscar Kuang-Sheng Lee2,6,7,8, Cheng-Wen Wu2,9 and Peng-Hui Wang1,2,3,10

1Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

3Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan

4Genomics Research Center, Academia Sinica, Taipei, Taiwan

5Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan

6Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan

7Taipei City Hospital, Taipei, Taiwan

8Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

9Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan

10Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

Correspondence to:

Peng-Hui Wang, email: phwang@vghtpe.gov.tw, phwang@ym.edu.tw, pongpongwang@gmail.com

Oscar Kuang-Sheng Lee, email: kslee@vghtpe.gov.tw, oscarlee9203@gmail.com

Cheng-Wen Wu, email: ken@ibms.sinica.edu.tw

Keywords: α2,3-sialyltransferases type I, epidermal growth factor receptor, epithelial ovarian cancer, soyasaponin I

Abbreviations: EOC: Epithelial ovarian cancer; EGFR: Epidermal growth factor receptor; SsaI: soyasaponin I; OS: overall survival; ST: sialyltransferase

Received: November 10, 2016    Accepted: February 10, 2017    Published: March 07, 2017

ABSTRACT

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.


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