Sialylation of FGFR1 by ST6Gal-I overexpression contributes to ovarian cancer cell migration and chemoresistance

被引:30
作者
Ou, Lingling [1 ]
He, Xiuzhen [2 ]
Liu, Naihua [3 ]
Song, Yuwei [1 ]
Li, Jinyuan [1 ]
Gao, Lvfen [1 ]
Huang, Xinke [1 ]
Deng, Zhendong [3 ]
Wang, Xiaoyu [1 ]
Lin, Shaoqiang [3 ,4 ]
机构
[1] Jinan Univ, Dept Stomatol, Affiliated Hosp 1, 613 West Huangpu Ave, Guangzhou 510632, Guangdong, Peoples R China
[2] Chongqing Three Gorges Med Coll, Chongqing 404120, Peoples R China
[3] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Integrated Tradit & Western Med Res Ctr, 19 Nonglinxia Rd, Guangzhou 510000, Guangdong, Peoples R China
[4] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
ovarian cancer; ST6Gal-I; FGFR1; chemoresistance; GROWTH-FACTOR RECEPTOR; ADHESION; INHIBITORS; SURVIVAL; FAK; SIALYLTRANSFERASE; GLYCOSYLATION; PROGRESSION; SENSITIVITY; RESISTANCE;
D O I
10.3892/mmr.2020.10951
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Fibroblast growth factor receptors (FGFRs) have been implicated in the malignant transformation and chemoresistance of epithelial ovarian cancer; however, the underlying molecular mechanisms are poorly understood. Increased sialyltransferase activity that enhances protein sialylation is an important post-translational process promoting cancer progression and malignancy. In the present study, alpha 2,6-sialyltransferase (ST6Gal-I) overexpression or knockdown cell lines were developed, and FGFR1 was examined to understand the effect of sialylation on migration and drug resistance, and the underlying mechanisms. It was identified that cells with ST6Gal-I overexpression had increased cell viability and migratory ability upon serum deprivation. Moreover, ST6Gal-I overexpression cells had strong resistance to paclitaxel, as demonstrated by low growth inhibition rate and cell apoptosis level. A mechanistic study showed that ST6Gal-I overexpression induced high alpha 2,6-sialylation of FGFR1 and increased the expression of phospho-ERK1/2 and phospho-focal adhesion kinase. Further study demonstrated that the FGFR1 inhibitor PD173047 reduced cell viability and induced apoptosis; however, ST6Gal-I overexpression decreased the anticancer effect of PD173047. In addition, ST6Gal-I overexpression attenuated the effect of Adriamycin on cancer cells. Collectively, these results suggested that FGFR1 sialylation plays an important role in cell migration and drug chemoresistance in ovarian cancer cells.
引用
收藏
页码:1449 / 1460
页数:12
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