Sialylation of FGFR1 by ST6Gal-I overexpression contributes to ovarian cancer cell migration and chemoresistance
Sialylation of FGFR1 by ST6Gal-I overexpression contributes to ovarian cancer cell migration and chemoresistance
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DOI：
10.3892/mmr.2020.10951
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发表时间：
2020-03-01
影响因子：
3.4
通讯作者：
Lin, Shaoqiang
中科院分区：
文献类型：
--
作者：
Ou, Lingling;He, Xiuzhen;Lin, Shaoqiang
成纤维细胞生长因子受体（FGFRs）与上皮性卵巢癌的恶性转化和化疗耐药有关；然而，人们对其潜在的分子机制知之甚少。唾液基转移酶活性的增加促进了蛋白质唾液基化，是促进癌症进展和恶性肿瘤的重要翻译后过程。在本研究中，培养了α 2,6-唾液基转移酶（ST6Gal-I）过表达或敲低的细胞系，并检测了FGFR1，以了解唾液基化对迁移和耐药的影响及其潜在机制。我们发现，st6gal - 1过表达的细胞在血清剥夺后细胞活力和迁移能力增加。此外，ST6Gal-I过表达细胞对紫杉醇具有较强的抗性，表现为低的生长抑制率和细胞凋亡水平。一项机制研究表明，ST6Gal-I过表达诱导FGFR1高α 2,6-唾液化，并增加磷酸化- erk1 /2和磷酸化-局灶黏附激酶的表达。进一步研究表明，FGFR1抑制剂PD173047可降低细胞活力并诱导细胞凋亡；而ST6Gal-I过表达会降低PD173047的抗癌作用。此外，ST6Gal-I过表达可减弱阿霉素对癌细胞的作用。总之，这些结果表明FGFR1唾液化在卵巢癌细胞的细胞迁移和药物耐药中起重要作用。
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.