The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2 (NDRG2)/gp130/STAT3 pathway
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Jiabei Wang1,*, Dalong Yin1,*, Changming Xie1,*, Tongsen Zheng1,*, Yingjian Liang 1, Xuehui Hong1, Zhaoyang Lu1, Xuan Song1, Ruipeng Song1, Haiyan Yang1, Boshi Sun1, Nishant Bhatta1, Xianzhi Meng1, Shangha Pan1, Hongchi Jiang1 and Lianxin Liu1,2
1 Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China
2 Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, China
* These authors contributed equally to this work
Lianxin Liu, email:
Keywords: Dp44mT; NDRG2; hepatocellular carcinoma; metastasis; STAT3
Received: June 09, 2014 Accepted: August 07, 2014 Published: August 08, 2014
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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