MAD2L1-mediated NANOG nuclear translocation: A critical factor in lung cancer chemoresistance

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-04-14 DOI:10.1016/j.cellsig.2025.111811

Hongye Zhao , Yongcun Liu , Longyu Zhu , Jingge Cheng , Yishuai Li

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引用次数: 0

Abstract

This study investigates the function of Mitotic Arrest Deficient 2 Like 1 (MAD2L1) and its role in facilitating NANOG nuclear localization, contributing to chemoresistance in lung cancer. Using both in vivo and in vitro models, we examined MAD2L1 expression in Carboplatin-resistant lung cancer cell lines. The study utilized gene knockdown and overexpression techniques to assess MAD2L1's role in chemoresistance and cell stemness, alongside co-expression analysis and fluorescence staining and CO-IP to explore MAD2L1 and NANOG interactions. Results showed a marked increase in MAD2L1 expression in resistant lung cancer cells, correlating with enhanced cell stemness. MAD2L1 knockdown heightened sensitivity to Carboplatin and reduced NANOG expression, while MAD2L1 overexpression led to increased resistance and stemness. Mechanistically, MAD2L1 facilitated NANOG's nuclear localization, with their co-expression linked to increased cell resistance and metastasis in vivo. These findings suggest that MAD2L1 enhances chemoresistance by promoting NANOG localization, offering insights into potential therapeutic targets for overcoming lung cancer chemoresistance.

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mad2l1介导的NANOG核易位：肺癌化疗耐药的关键因素

本研究探讨了有丝分裂抑制缺陷2样1 （MAD2L1）的功能及其在促进NANOG核定位、促进肺癌化疗耐药中的作用。使用体内和体外模型，我们检测了MAD2L1在卡铂耐药肺癌细胞系中的表达。该研究利用基因敲低和过表达技术来评估MAD2L1在化疗耐药和细胞干细胞性中的作用，并利用共表达分析、荧光染色和CO-IP来探索MAD2L1和NANOG的相互作用。结果显示，在耐药肺癌细胞中，MAD2L1的表达显著增加，与细胞干细胞增强相关。MAD2L1敲低增加了对卡铂的敏感性，降低了NANOG的表达，而MAD2L1过表达导致抗性和干性增加。在机制上，MAD2L1促进了NANOG的核定位，它们的共表达与体内细胞抵抗和转移的增加有关。这些发现表明，MAD2L1通过促进NANOG定位来增强化疗耐药，为克服肺癌化疗耐药的潜在治疗靶点提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.