NID1, a new regulator of EMT required for metastasis and chemoresistance of ovarian cancer cells.
NID1, a new regulator of EMT required for metastasis and chemoresistance of ovarian cancer cells.
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NID1，卵巢癌细胞转移和化疗耐药所需的 EMT 新调节因子
DOI：
10.18632/oncotarget.16145
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发表时间：
2017-05-16
期刊：
影响因子：
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通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Zhou Y;Zhu Y;Fan X;Zhang C;Wang Y;Zhang L;Zhang H;Wen T;Zhang K;Huo X;Jiang X;Bu Y;Zhang Y
Nidogen-1(NID1)在我们先前的研究中被确定为一种新的卵巢癌候选诊断生物标志物。然而，NID1在卵巢癌发病机制中的作用尚不清楚。在本研究中，我们证明了NID1是一种间充质相关基因，其高表达与卵巢癌患者总生存期的缩短显著相关。NID1在OVCAR-3细胞中的异位表达表现为上皮-间充质转化(EMT)表型，伴随着移动性、侵袭性和顺铂耐受性的增强，而NID1的敲除足以将HY细胞转化为上皮表型，其移动性、侵袭性和顺铂耐受性降低。机制研究表明，NID1激活ERK/MAPK信号通路促进EMT。总之，我们的发现揭示了NID1促进卵巢癌转移和化疗耐药的分子机制，并为抑制NID1在卵巢癌中的治疗潜力提供了理论基础。
Nidogen-1 (NID1) has been identified as a novel candidate diagnostic biomarker of ovarian cancer in our previous study. Nevertheless, the role of NID1 in the pathogenesis of ovarian cancer is unclear. In the present study, we demonstrated that NID1 was a mesenchymal associated gene and its high expression was significantly correlated with shorter overall survival of ovarian cancer patients. The ectopic expression of NID1 in OVCAR-3 cells revealed a epithelial-mesenchymal transition (EMT) phenotype accompanied by enhancement of motility, invasiveness and cisplatin resistance, whereas the knockdown of NID1 was sufficient to convert HEY cells into epithelial phenotype with decreased capability of motility, invasiveness and cisplatin resistance. Mechanistic studies disclosed that NID1 activated ERK/MAPK signaling pathway to promote EMT. Collectively, our findings have uncovered the molecular mechanisms of NID1 in promoting ovarian cancer metastasis and chemoresistance, and provide a rationale for the therapeutic potential of NID1 suppression in ovarian cancer.