β3GnT8 regulates oxaliplatin resistance by altering integrin β1 glycosylation in colon cancer cells.
β3GnT8 regulates oxaliplatin resistance by altering integrin β1 glycosylation in colon cancer cells.
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DOI：
10.3892/or.2018.6243
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发表时间：
2018-04
期刊：
影响因子：
4.2
通讯作者：
Li Shen;Xiaoxian Dong;Yingying Wang;Li Qiu;Feng Peng;Zhiguo Luo
中科院分区：
文献类型：
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作者：
Li Shen;Xiaoxian Dong;Yingying Wang;Li Qiu;Feng Peng;Zhiguo Luo
糖基化改变与耐药的关系已成为肿瘤生物学研究的热点。本研究的目的是探讨糖链和糖基因的改变参与人结肠癌细胞奥沙利铂耐药。使用凝集素微阵列的聚糖组成和FITC-凝集素结合的聚糖分析，我们发现，聚乳糖胺型N-聚糖显着增加奥沙利铂耐药SW 620 R细胞。使用实时PCR定量糖原，我们靶向β-1，3-N-乙酰葡糖胺转移酶8（β 3GnT8），它在SW620 R细胞中过表达。使用RNA干扰策略，我们发现SW620 R细胞中β 3GnT8的沉默导致对奥沙利铂的化疗敏感性增加。相反，β 3GnT8在SW620细胞中的工程过表达增强了对奥沙利铂的耐药性。进一步的数据显示，操纵β 3GnT8能够修饰整合素β 1上的聚乳糖胺链，并调节整合素β 1下游信号通路。这些结果表明，β 3GnT8可能通过改变整合素β 1的糖基化在结肠癌细胞奥沙利铂耐药的发展中发挥关键作用。这些发现可能对克服结肠癌的耐药性有价值。
Correlations between drug resistance and glycosylation changes have been analyzed intensively in the field of tumor biology. The present study was aimed to investigate the glycan and glycogene alterations involved in oxaliplatin resistance in human colon cancer cells. Using the lectin microarray for glycan composition and FITC-lectin binding for glycan profiling, we found that polylactosamine-type N-glycans were significantly increased in oxaliplatin-resistant SW620R cells. Using real-time PCR for quantification of glycogenes, we targeted β-1,3-N-acetylglucosaminyltransferase 8 (β3GnT8), which was overexpressed in SW620R cells. Using an RNA interference strategy, we revealed that the silencing of β3GnT8 in SW620R cells resulted in increased chemosensitivity to oxaliplatin. Conversely, the engineered overexpression of β3GnT8 in SW620 cells enhanced resistance to oxaliplatin. Further data revealed that manipulation of β3GnT8 was able to modify polylactosamine chains on integrin β1 and to regulate the integrin β1 downstream signaling pathway. These results revealed that β3GnT8 may play a key role in the development of oxaliplatin resistance in colon cancer cells possibly through the alteration of the glycosylation of integrin β1. These findings may be valuable for overcoming drug resistance in colon cancer.