蜗牛
生物
上皮-间质转换
癌症研究
转移
转录因子
肿瘤进展
运动性
癌症
细胞生物学
基因
遗传学
生态学
作者
Minhui Zhu,Fang‐Fang Yin,Xiaoyu Fan,Jing Wei,R Chen,L Liu,L Zhang,Y Liu,Yingchao Liang,Fanping Bu,Xin Tong,Hongliang Zheng,Jian Zhao,Yingjun Guo
出处
期刊:Oncogene
[Springer Nature]
日期:2014-03-31
卷期号:34 (11): 1420-1431
被引量:28
摘要
The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to tumor recurrence and metastases. Recently, epithelial-mesenchymal transition (EMT) has been implicated in tumor invasion and metastasis. However, the underlying molecular mechanisms are yet to be elucidated. Here, we show that 30-kDa Tat-interacting protein (TIP30), also called CC3, is significantly downregulated during transforming growth factor-β-induced EMT. In our in vitro and in vivo studies, we show that decreased TIP30 expression leads to EMT, as well as enhanced motility and invasion of HCC cells. Also, increased self-renewal ability and chemotherapeutic resistance are observed with TIP30 depletion. Moreover, Snail is one of the key transcription factors promoting EMT, and overexpression of TIP30 greatly decreased nucleic accumulation in Snail through the regulation of intracellular localization. Small interfering RNAs targeting Snail attenuated EMT and tumor-initiating properties induced by TIP30 deficiency. We further confirmed that TIP30 competitively interrupted the interaction of Snail with importin-β2 to block the nuclear import of Snail. Consistently, TIP30 expression significantly correlates with E-cadherin expression in HCC patients. TIP30 or combination of E-cadherin is a powerful marker in predicting the prognosis of HCC. Taken together, our results suggest a novel and critical role of TIP30 involved in HCC progression and aggressiveness.
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