title: HMGB-1 induces cell motility and α5β1 integrin expression in human chondrosarcoma cells.
abstract: Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. High mobility group box chromosomal protein 1 (HMGB)-1 is a widely studied, ubiquitous nuclear protein that is present in eukaryotic cells, and plays a crucial role in inflammatory response. However, the effects of HMGB-1 on human chondrosarcoma cells are largely unknown. In this study, we found that HMGB-1 increased the migration and the expression of α5β1 integrin in human chondrosarcoma cells. Transfection of cells with receptor for advanced glycation end products (RAGE) receptor siRNA reduced HMGB-1-induced cell migration and integrin expression. Activations of phosphatidylinositol 3-kinase (PI3K), Akt, and AP-1 pathways after HMGB-1 treatment were demonstrated, and HMGB-1-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and AP-1 cascades. Taken together, our results indicated that HMGB-1 enhances the migration of chondrosarcoma cells by increasing α5β1 integrin expression through the RAGE receptor/PI3K/Akt/c-Jun/AP-1 signal transduction pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan. chtang@mail.cmu.edu.tw
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Keng
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Liu
mesh_terms: D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002813:Chondrosarcoma / Q000473:pathology*; D024243:HMGB1 Protein / Q000502:physiology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology
chemical_list: D024243:HMGB1 Protein; D039081:Integrin alpha5beta1; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D018808:Transcription Factor AP-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt