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NEDD4 is involved in acquisition of epithelial-mesenchymal transition in cisplatin-resistant nasopharyngeal carcinoma cells

机译:NEDD4参与采集顺铂抗性鼻咽癌细胞中的上皮 - 间充质转变

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摘要

Nasopharyngeal carcinoma (NPC) is a highly invasive head-neck cancer derived from the nasopharyngeal epithelium, mainly prevalent in southern China and Southeast Asia. Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard administrations applied in the treatment of NPC. However, resistance to chemotherapeutic drugs has recently become more common, resulting in worse treatment outcome for NPC therapy. To elucidate the underlying molecular basis of drug resistance to DDP in NPC cells, we examined the morphocytology, cell motility and molecular changes in DDP-resistant NPC cells with respect to epithelial-mesenchymal transition (EMT) features. We found that EMT is closely associated with DDP-induced drug resistance in NPC cells, as DDP-resistant cells displayed morphological and molecular markers changes consistent with EMT. Wound healing and Transwell Boyden chamber assays revealed an enhanced migration and invasion potential in DDP-resistant NPC cells. Mechanistically, upregulation of NEDD4 was observed to relate to EMT in DDP-resistant cells. More importantly, depletion of NEDD4 in resistant cells led to a partial reversion of EMT phenotypes to MET characteristics. These data suggest that NEDD4 is largely involved in EMT features and chemoresistance of NPC cancer cells. NEDD4 could be a novel therapeutic target to overcome drug resistance in successful administrations of NPC.
机译:鼻咽癌(NPC)是源自鼻咽上皮的高度侵袭性头颈癌,主要是中国南部和东南亚的普遍存在。放射疗法和佐剂顺铂(DDP)化疗是应用于治疗NPC的标准施用。然而,对化学治疗药物的抗性最近变得更加常见,导致NPC治疗的治疗结果差。为了阐明NPC细胞中对DDP的耐药性的潜在分子基础,我们研究了关于上皮 - 间充质转换(EMT)特征的DDP抗性NPC细胞中的形态细胞学,细胞运动和分子变化。我们发现EMT与NPC细胞中的DDP诱导的耐药性密切相关,因为DDP抗性细胞显示形态学和分子标记与EMT一致的变化。伤口愈合和Transwell Boyden室测定显示DDP抗性NPC细胞中增强的迁移和侵袭电位。机械地,观察到NEDD4的上调涉及DDP抗性细胞中的EMT。更重要的是,耐药细胞中NEDD4的耗尽导致EMT表型的部分逆转,以满足特征。这些数据表明NEDD4主要参与NPC癌细胞的EMT特征和化学抑制。 NEDD4可以是一种新的治疗靶标,以克服NPC的成功施用耐药性。

著录项

  • 来源
    《Cell cycle》 |2017年第9期|共10页
  • 作者单位

    Sun Yat Sen Univ Dept Otorhinolaryngol Head &

    Neck Surg Affiliated Hosp 3 Guangzhou Guangdong;

    Sun Yat Sen Univ Dept Radiat Oncol Affiliated Hosp 5 Zhuhai Peoples R China;

    Sun Yat Sen Univ Sun Yat Sen Mem Hosp Dept Otolaryngol Guangzhou Guangdong Peoples R China;

    Sun Yat Sen Univ Dept Radiat Oncol Affiliated Hosp 5 Zhuhai Peoples R China;

    Sun Yat Sen Univ Dept Orthopaed Affiliated Hosp 5 Zhuhai Peoples R China;

    Sun Yat Sen Univ Dept Otorhinolaryngol Head &

    Neck Surg Affiliated Hosp 5 Zhuhai Peoples R China;

    Sun Yat Sen Univ Dept Otorhinolaryngol Head &

    Neck Surg Affiliated Hosp 3 Guangzhou Guangdong;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    drug resistance; EMT; Nasopharyngeal carcinoma; NEDD4;

    机译:耐药;EMT;鼻咽癌;NEDD4;

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