title: High-mobility group box 1: a novel inducer of the epithelial-mesenchymal transition in colorectal carcinoma.
abstract: Proinflammatory cytokine high-mobility group box 1 (HMGB1) mediates critical processes of tumour metastasis. Because the epithelial-to-mesenchymal transition (EMT) is a key player in metastasis, the aim of this study was to determine whether and through which mechanism HMGB1 induces EMT in colorectal carcinoma. The direct treatment of cells with recombinant human HMGB1 induced alterations in the epithelial morphology consistent with the EMT and enhanced cell migration through a process mediated by the receptor for advanced glycation end-products (RAGE). The levels of Snail and phospho-NF-κB were upregulated during the HMGB1-induced EMT, and these effects were reversed by inhibiting Snail and NF-κB. In addition, HMGB1 increased the expression of MMP-7 but not that of MMP-9, and this effect was also regulated by Snail/NF-κB signalling. Collectively, these findings indicate that HMGB1 acts as a potent driver of cancer EMT through the RAGE/Snail/NF-κB signalling pathways accompanied by the activation of MMP-7, thereby suggest the feasibility of targeting HMGB1 for the treatment of tumour metastasis.
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
authors.forename: Lingyin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: lxb_1969@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
authors.forename: Yingxuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fang
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
authors.forename: Zhizheng
authors.initials: Z
authors.lastname: Ge
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D024243:HMGB1 Protein / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D020783:Matrix Metalloproteinase 7
keywords: Colorectal carcinoma; Epithelial–mesenchymal transition; High-mobility group box 1; Matrix metalloproteinase-7