title: The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2 (NDRG2)/gp130/STAT3 pathway.
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.
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China. These authors contributed equally to this work.
authors.forename: Jiabei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China. These authors contributed equally to this work.
authors.forename: Dalong
authors.initials: D
authors.lastname: Yin
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China. These authors contributed equally to this work.
authors.forename: Changming
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China. These authors contributed equally to this work.
authors.forename: Tongsen
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Song
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Boshi
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Nishant
authors.initials: N
authors.lastname: Bhatta
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Hongchi
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province, China. 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.
authors.forename: Lianxin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013882:Thiosemicarbazones / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C494199:IL6ST protein, human; D007502:Iron Chelating Agents; C466228:NDRG2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C508960:TGFB1 protein, human; D013882:Thiosemicarbazones; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; C539263:di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; D050822:Cytokine Receptor gp130