The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2 (NDRG2)/gp130/STAT3 pathway

نویسندگان

  • Jiabei Wang
  • Dalong Yin
  • Changming Xie
  • Tongsen Zheng
  • Yingjian Liang
  • Xuehui Hong
  • Zhaoyang Lu
  • Xuan Song
  • Ruipeng Song
  • Haiyan Yang
  • Boshi Sun
  • Nishant Bhatta
  • Xianzhi Meng
  • Shangha Pan
  • Hongchi Jiang
  • Lianxin Liu
چکیده

Here we showed that hepatocellular carcinoma (HCC) cell lines with high metastatic potential had low levels of NDRG2. The iron chelator Dp44mT up-regulated NDRG2, suppressed epithelial-mesenchymal transition (EMT) and inhibited tumor metastasis in HCC having high metastatic potential. Also Dp44mT attenuated the TGF-β1-induced EMT in HCC having low metastatic potential. In agreement, silencing endogenous NDRG2 with shNDRG2 in HCC cells attenuated the effect of Dp44mT. We showed that the NDRG2/gp130/STAT3 pathway can mediate Dp44mT effects. In agreement, we found that a combination of NDRG2 expression and p-STAT3 levels is a strong predictor of prognosis in HCC patients. We suggest that up-regulation of NDRG2 by Dp44mT is a promising therapeutic approach in HCC.

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عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2014