Oncotarget 2014-09-30

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

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

Index: Oncotarget 5(18) , 8478-91, (2014)

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Abstract

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.