Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA.
Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA.
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Nipped-B 样蛋白通过上调 PUMA 使食管鳞状细胞癌细胞对顺铂敏感
DOI：
10.1177/1533033820960726
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发表时间：
2020-01
影响因子：
2.8
通讯作者：
Hong L
中科院分区：
文献类型：
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作者：
Zhang S;Zhou Y;Wang Q;Donahue K;Feng J;Yao Y;Chen A;Li X;Hong L
Nipped-B-like蛋白作为细胞分裂时染色体分离的粘附素加载因子起着关键作用。越来越多的证据表明，这种蛋白质的改变参与了人类肿瘤的发生，特别是在调节化疗药物的反应。然而，Nipped-B样蛋白在食管鳞状细胞癌中的作用仍不清楚。在这项研究中，我们研究了Nipped-B样蛋白在食管鳞癌顺铂敏感性调节中的相关性。Nipped-B样蛋白的异位表达抑制了内源性Nipped-B样蛋白表达水平低的科洛-680 N细胞的生长，并增加了对食管鳞癌患者常用化疗药物顺铂的敏感性。相反，Nipped-B样蛋白的缺失刺激了具有高水平蛋白的EC 9706和Eca-109细胞的生长，并导致对顺铂的抗性。P53上调的细胞凋亡调节剂，其在多种癌症中顺铂敏感性的调节中是必需的，充当Nipped-B样蛋白的下游效应物。这种促凋亡蛋白在Nipped-B样蛋白过表达的食管鳞状细胞癌细胞中的恢复有效地增加了顺铂的敏感性。相反，沉默P53上调的凋亡调节因子在Nipped-B样蛋白缺失的食管鳞状细胞癌中使细胞对顺铂耐药。此外，Nipped-B-like蛋白可以直接结合到P53上调的凋亡调节因子的启动子区。总之，我们的研究解决了Nipped-B样蛋白参与食管鳞状细胞癌的发展，并通过调节P53上调的细胞凋亡调节剂来调节顺铂的敏感性。
Nipped-B-like protein plays a pivotal role as a cohesin loading factor in the segregation of chromosomes when cells divide. Accumulating evidence indicates that alterations of this protein are involved in human carcinogenesis, especially in the regulation of chemotherapeutic drug response. However, the role of Nipped-B-like protein in esophageal squamous cell carcinoma remains unknown. In this study, we investigated the relevance of Nipped-B-like protein in the regulation of cisplatin sensitivity in esophageal squamous cell carcinoma. Ectopic expression of Nipped-B-like protein inhibited the growth of COLO-680N cells with low endogenous expression levels of Nipped-B-like protein, and increased sensitivity to cisplatin, a commonly used chemotherapy drug for patients with esophageal squamous cell carcinoma. In contrast, loss of Nipped-B-like protein stimulated the growth of EC9706 and Eca-109 cells with high levels of the protein, and resulted in resistance to cisplatin. P53-upregulated modulator of apoptosis, which is essential in the modulation of cisplatin sensitivity in a variety of cancers, acts as a downstream effector of Nipped-B-like protein. Restoration of this pro-apoptotic protein in Nipped-B-like protein-overexpressing esophageal squamous cell carcinoma cells effectively increased cisplatin sensitivity. Conversely, the silencing of P53-upregulated modulator of apoptosis in Nipped-B-like protein-depleted esophageal squamous cell carcinoma rendered cells resistant to cisplatin. Moreover, Nipped-B-like protein could bind directly to the promoter region of P53-upregulated modulator of apoptosis. In summary, our study addresses the involvement of Nipped-B-like protein in the development of esophageal squamous cell carcinoma, and the modulation of cisplatin sensitivity via regulation of P53-upregulated modulator of apoptosis.
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影响因子：
24.3
作者：
Correia, Ana Luisa;Bissell, Mina J.
通讯作者：
Bissell, Mina J.
MiR-222 靶向 PUMA 以提高 UM1 细胞对顺铂的敏感性。
影响因子：
5.6
作者：
Jiang F;Zhao W;Zhou L;Liu Z;Li W;Yu D
通讯作者：
Yu D
影响因子：
64.5
作者：
Haarhuis JHI;van der Weide RH;Blomen VA;Yáñez-Cuna JO;Amendola M;van Ruiten MS;Krijger PHL;Teunissen H;Medema RH;van Steensel B;Brummelkamp TR;de Wit E;Rowland BD
通讯作者：
Rowland BD
影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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