MGAT4A/Galectin9-Driven N-Glycosylation Aberration as a Promoting Mechanism for Poor Prognosis of Endometrial Cancer with TP53 Mutation
文献类型：期刊论文
| 作者 | Zhu, Zhen2,10,11; Sun, Jingya9; Xu, Weiqing8; Zeng, Qinghe9; Feng, Hanyi7,9; Zang, Lijuan8; He, Yinyan1,6; He, Xiao7,9; Sheng, Na10; Ren, Xuelian5 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2024-11-11 |
| 页码 | 19 |
| 关键词 | endometrial cancer
glucose metabolism
MGAT4A
|
| DOI | 10.1002/advs.202409764 |
| 通讯作者 | Huang, Ruimin(rmhuang@simm.ac.cn) ; Yan, Jun(yan_jun@fudan.edu.cn) |
| 英文摘要 | Emerging evidence recognizes aberrant glycosylation as the malignant characteristics of cancer cells, but little is known about glycogenes' roles in endometrial carcinoma (EC), especially the most aggressive subtype carrying TP53 mutations. Using unsupervised hierarchical clustering, an 11-glycogene cluster is identified to distinguish an EC subtype associated with frequent TP53 mutation and worse prognosis. Among them, MGAT4A (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A) emerges as the most consistently overexpressed glycogene, contributing to EC aggressiveness. In the presence of galectin-9, MGAT4A increases EC cell proliferation and invasion via promoting glucose metabolism. N-glycoproteomics further revealed GLUT1, a glucose transporter, as a glycoprotein modified by MGAT4A. Binding of galectin-9 to the MGAT4A-branched N-glycan on GLUT1 enhances its cell membrane distribution, leading to glucose uptake increase. In addition, oncogenic mutations of TP53 gene in EC cells upregulate MGAT4A expression by disrupting the regulatory oversight exerted by wild-type p53 on tumor-suppressive miRNAs, including miR-34a and miR-449a/b. The findings highlight a new molecular mechanism involving MGAT4A-regulated N-glycosylation on the key regulator of glucose metabolism in p53 mutants-driven EC aggressiveness, which may provide a strategic avenue to combat advanced EC. |
| WOS关键词 | ACETYLGLUCOSAMINYLTRANSFERASE-IVA ; BREAST-CANCER ; GLUT1 ; GLYCOLYSIS ; SURVIVAL ; CELLS ; RISK ; IDENTIFICATION ; EXPRESSION ; MIGRATION |
| 资助项目 | National Natural Science Foundation of China ; Shanghai Municipal Science and Technology Major Project ; Science and Technology Commission of Shanghai Municipality[21140903700] ; [82073234] ; [82172001] ; [81902968] ; [82203119] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001354093700001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/314409]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, Ruimin; Yan, Jun |
| 作者单位 | 1.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Obstet & Gynecol, Shanghai 200072, Peoples R China 2.Fudan Univ, Shanghai Pudong Hosp, Pudong Med Ctr, Ctr Med Res & Innovat, Shanghai 200032, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 6.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Obstet & Gynecol, Sch Med, Shanghai 200080, Peoples R China 7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 8.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Pathol, Shanghai 200080, Peoples R China 9.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 10.Nanjing Univ, Model Anim Res Ctr, Nanjing 210061, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Zhen,Sun, Jingya,Xu, Weiqing,et al. MGAT4A/Galectin9-Driven N-Glycosylation Aberration as a Promoting Mechanism for Poor Prognosis of Endometrial Cancer with TP53 Mutation[J]. ADVANCED SCIENCE,2024:19. |
| APA | Zhu, Zhen.,Sun, Jingya.,Xu, Weiqing.,Zeng, Qinghe.,Feng, Hanyi.,...&Yan, Jun.(2024).MGAT4A/Galectin9-Driven N-Glycosylation Aberration as a Promoting Mechanism for Poor Prognosis of Endometrial Cancer with TP53 Mutation.ADVANCED SCIENCE,19. |
| MLA | Zhu, Zhen,et al."MGAT4A/Galectin9-Driven N-Glycosylation Aberration as a Promoting Mechanism for Poor Prognosis of Endometrial Cancer with TP53 Mutation".ADVANCED SCIENCE (2024):19. |
入库方式： OAI收割
来源：上海药物研究所
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