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唾液酸化-Tn抗原合成酶基因在缺氧条件下调节前列腺癌细胞的迁移-增殖二分法。

The sialyl-Tn antigen synthase genes regulates migration-proliferation dichotomy in prostate cancer cells under hypoxia.

作者信息

Yamamoto Daiki, Hongo Hiroshi, Kosaka Takeo, Aoki Natsumi, Oya Mototsugu, Sato Toshinori

机构信息

Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 223-8522, Kanagawa, Japan.

Department of Urology, Keio University School of Medicine, 160-8582, Tokyo, Japan.

出版信息

Glycoconj J. 2023 Apr;40(2):199-212. doi: 10.1007/s10719-023-10104-z. Epub 2023 Feb 18.

DOI:10.1007/s10719-023-10104-z
PMID:36806956
Abstract

A low-oxygen (hypoxia) tumor microenvironment can facilitate chemotherapy and radiation therapy resistance in tumors and is associated with a poor prognosis. Hypoxia also affects PCa (prostate cancer) phenotype transformation and causes therapeutic resistance. Although O-glycans are known to be involved in the malignancy of various cancers under hypoxia, the expression and function of O-glycans in PCa are not well understood. In this study, the saccharide primer method was employed to analyze O-glycan expression in PCa cells. Results showed that the expression of sTn antigens was increased in PCa cells under hypoxia. Furthermore, it was found that ST6GalNAc1, the sTn antigen synthase gene, was involved in the migration-proliferation dichotomy and drug resistance in PCa cells under hypoxia. The results of this study will contribute to the development of novel diagnostic markers and drug targets for PCa under hypoxia.

摘要

低氧(缺氧)肿瘤微环境可促进肿瘤对化疗和放疗的耐药性,并与预后不良相关。缺氧还会影响前列腺癌(PCa)的表型转化并导致治疗耐药性。尽管已知O-聚糖在缺氧情况下参与各种癌症的恶性发展,但O-聚糖在PCa中的表达和功能尚未得到充分了解。在本研究中,采用糖引物法分析PCa细胞中O-聚糖的表达。结果显示,缺氧条件下PCa细胞中sTn抗原的表达增加。此外,还发现sTn抗原合成酶基因ST6GalNAc1参与了缺氧条件下PCa细胞的迁移-增殖二分法和耐药性。本研究结果将有助于开发针对缺氧条件下PCa的新型诊断标志物和药物靶点。

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本文引用的文献

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Glycobiology. 2022 Sep 19;32(10):897-908. doi: 10.1093/glycob/cwac044.
2
Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy.缺氧诱导三阴性乳腺癌中 HIF1α 依赖性表观遗传脆弱性,从而导致免疫效应功能障碍和对抗 PD-1 免疫治疗的耐药性。
Nat Commun. 2022 Jul 15;13(1):4118. doi: 10.1038/s41467-022-31764-9.
3
In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
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Carbohydr Res. 2022 Jan;511:108495. doi: 10.1016/j.carres.2021.108495. Epub 2021 Dec 30.
4
Characterizing Intercellular Communication of Pan-Cancer Reveals SPP1+ Tumor-Associated Macrophage Expanded in Hypoxia and Promoting Cancer Malignancy Through Single-Cell RNA-Seq Data.通过单细胞RNA测序数据对泛癌的细胞间通讯进行表征,揭示了在缺氧状态下扩增并通过SPP1促进癌症恶性进展的SPP1+肿瘤相关巨噬细胞。
Front Cell Dev Biol. 2021 Oct 5;9:749210. doi: 10.3389/fcell.2021.749210. eCollection 2021.
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