史美云

个人信息Personal Information

副教授

硕士生导师

性别:女

毕业院校:吉林大学

学位:博士

所在单位:化工海洋与生命学院

学科:药理学

办公地点:F03-311

联系方式:0427-2631427

电子邮箱:shimy@dlut.edu.cn

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O-GlcNAc elevation through activation of the hexosamine biosynthetic pathway enhances cancer cell chemoresistance.

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论文类型:期刊论文

发表时间:2018-01-01

发表刊物:Cell death & disease

收录刊物:PubMed、SCIE、Scopus

卷号:9

期号:5

ISSN号:2041-4889

摘要:Chemoresistance has become a major obstacle to the success of cancer therapy, but the mechanisms underlying chemoresistance are not yet fully understood. O-GlcNAcylation is a post-translational modification that is regulated by the hexosamine biosynthetic pathway (HBP) and has an important role in a wide range of cellular functions. Here we assessed the role of O-GlcNAcylation in chemoresistance and investigated the underlying cellular mechanisms. The results showed that the HBP has an important role in cancer cell chemoresistance by regulating O-GlcNAcylation. An increase in the levels of O-GlcNAcylation indicates an increased resistance of cancer cells to chemotherapy. Acute treatment with doxorubicin (DOX) or camptothecin (CPT) induced O-GlcNAcylation through HBP activation. In fact, the chemotherapy agents activated the AKT/X-box-binding protein 1 (XBP1) axis and then induced the HBP. Furthermore, the observed elevation of cellular O-GlcNAcylation led to activation of survival signalling pathways and chemoresistance in cancer cells. Finally, suppression of O-GlcNAcylation reduced the resistance of both established and primary cancer cells to chemotherapy. These results provide significant novel insights regarding the important role of the HBP and O-GlcNAcylation in regulating cancer chemoresistance. Thus, O-GlcNAc inhibition might offer a new strategy for improving the efficacy of chemotherapy.