Mucin 21 confers resistance to apoptosis in an O-glycosylation-dependent manner.
Mucin 21 confers resistance to apoptosis in an O-glycosylation-dependent manner.
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粘蛋白21以O-糖基化依赖性方式赋予对细胞凋亡的抗性。
DOI：
10.1038/s41420-022-01006-4
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发表时间：
2022-04-11
影响因子：
7
通讯作者：
Irimura, Tatsuro
中科院分区：
文献类型：
--
作者：
Tian, Yuan;Denda-Nagai, Kaori;Tsukui, Tatsuya;Ishii-Schrade, Katrin B.;Okada, Kyoko;Nishizono, Yoshihiro;Matsuzaki, Kosuke;Hafley, Margarete;Bresalier, Robert S.;Irimura, Tatsuro
高度糖基化的粘蛋白保护上皮细胞表面免受外部损伤，并与癌细胞的恶性行为有关。然而，粘蛋白上的碳水化合物链在细胞保护过程中的重要性尚未完全了解。在这里，我们研究了人粘蛋白-21（MUC 21）表达对细胞凋亡易感性的影响。MUC 21转染HEK 293细胞后，在含有依托泊苷的培养基中或在紫外线照射后，凋亡细胞的数量减少。我们使用中国仓鼠卵巢（CHO）细胞变体来研究MUC 21糖基化在抗凋亡中的重要性。当MUC 21在CHO-K1细胞中表达时，它被唾液酸T抗原糖基化，并且细胞显示对依托泊苷诱导的凋亡的抗性。MUC 21转染到Lec 2细胞中，一种缺乏聚糖唾液酸化的CHO细胞变体，揭示了非唾液酸化T抗原的存在也使细胞对依托泊苷诱导的细胞凋亡具有抗性。将MUC 21转染到ldlD细胞中，并通过补充培养基来操纵糖基化。未补充的细胞和补充N-乙酰半乳糖胺的细胞对依托泊苷诱导的细胞凋亡没有抵抗力。相反，这些细胞补充N-乙酰半乳糖胺加半乳糖表达唾液酸T抗原，并表现出对依托泊苷诱导的细胞凋亡的抗性。最后，在HEK 293细胞的MUC 21转染子中，半乳糖凝集素-3敲低并不显著影响MUC 21依赖的凋亡抗性诱导。结果表明，T抗原与或不与唾液酸是必不可少的MUC 21的抗凋亡作用。粘蛋白21（MUC 21）是一种保护鳞状上皮的大糖蛋白。粘蛋白中的聚糖变化发生在癌细胞中，并被认为有助于恶性进展。我们报告了MUC 21的糖型依赖性抗凋亡作用。各种MUC 21糖型在HEK 293和CHO细胞中表达。使用依托泊苷或UV照射诱导细胞凋亡。具有以半乳糖/唾液酸终止的聚糖的MUC 21抑制细胞凋亡;不具有聚糖或N-乙酰半乳糖胺的MUC 21不抑制细胞凋亡。
Highly glycosylated mucins protect epithelial surfaces from external insults and are related to malignant behaviors of carcinoma cells. However, the importance of carbohydrate chains on mucins in the process of cellular protection is not fully understood. Here, we investigated the effect of human mucin-21 (MUC21) expression on the susceptibility to apoptosis. MUC21 transfection into HEK293 cells decreased the number of apoptotic cells in culture media containing etoposide or after ultraviolet light irradiation. We used Chinese hamster ovary (CHO) cell variants to investigate the importance of MUC21 glycosylation in the resistance to apoptosis. When MUC21 was expressed in CHO-K1 cells, it was glycosylated with sialyl T-antigen and the cells showed resistance to etoposide-induced apoptosis. MUC21 transfection into Lec2 cells, a variant of CHO cells lacking sialylation of glycans, revealed that the presence of nonsialylated T-antigen also renders cells resistant to etoposide-induced apoptosis. MUC21 was transfected into ldlD cells and the glycosylation was manipulated by supplementation to the medium. Nonsupplemented cells and cells supplemented with N-acetylgalactosamine showed no resistance to etoposide-induced apoptosis. In contrast, these cells supplemented with N-acetylgalactosamine plus galactose expressed sialyl T-antigen and exhibited resistance to etoposide-induced apoptosis. Finally, galectin-3 knockdown in MUC21 transfectants of HEK293 cells did not significantly affect MUC21-dependent induction of apoptosis resistance. The results suggest that T-antigen with or without sialic acid is essential to the antiapoptotic effect of MUC21. Mucin 21 (MUC21) is a large glycoprotein that protects squamous epithelia. Glycan changes in mucins occur in cancer cells and are thought to contribute to malignant progression. We report glycoform-dependent antiapoptotic effects of MUC21. Various MUC21 glycoforms were expressed in HEK293 and CHO cells. Apoptosis was induced using etoposide or UV exposure. MUC21 with glycans terminated with galactose/sialic acid inhibited apoptosis; MUC21 with no glycans or N-acetylgalactoseamine did not.
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MUC1粘蛋白的表达与肾细胞癌患者的术后生存呈负相关。
影响因子：
8.8
作者：
Fujita, K;Denda, K;Yamamoto, M;Matsumoto, T;Fujime, M;Irimura, T
通讯作者：
Irimura, T
影响因子：
6.4
作者：
HILKENS, J;BUIJS, F;VANDERVALK, M
通讯作者：
VANDERVALK, M
影响因子：
64.5
作者：
KINGSLEY, DM;KOZARSKY, KF;KRIEGER, M
通讯作者：
KRIEGER, M
DOI：
10.1016/j.bbrc.2008.12.153
发表时间：
2009-02-06
影响因子：
3.1
作者：
Lin, Chi-Iou;Whang, Edward E.;Ruan, Daniel T.
通讯作者：
Ruan, Daniel T.
DOI：
10.1093/jnci/50.5.1259
发表时间：
1973-01-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
KLEIN, G;FRIBERG, S;HARRIS, H
通讯作者：
HARRIS, H