title: HMGB1-induced autophagy in Schwann cells promotes neuroblastoma proliferation.
abstract: Neuroblastoma inflicts mostly on children, and the pathogenesis remains elusive. Clinical diagnosis and therapeutic approaches are still on the incipient stage, so further understanding of the molecular and cellular mechanisms of the disease is necessary. Inflammation has been commonly regarded as a hallmark in tumorigenesis and development, and we identified a new inflammatory factor, HMGB1, is considerably increased in neuroblastoma. Our study shows that HMGB1 induces autophagy in Schwann cells through activation of TLR4, and knockdown of TLR4 obviates the HMGB1-induced autophagy. The HMGB1-induced autophagy is through classical pathway, as deficiency of Beclin 1 deprived autophagy in Schwann cells. Coculture of neuroblastoma with Schwann cells pretreated with HMGB1 promoted the proliferation of neuroblastoma cells, and if Beclin 1 is knocked down in Schwann cells, no promotion effects is observed. Taken together, our study demonstrates that HMGB1-induced autophagy in Schwann cells contributes to neuroblastoma cell proliferation, thus providing a potential therapeutic approach on neuroblastoma development.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China ; Department of Neurosurgery, The First People's Hospital of Shangqiu Shangqiu 476005, Henan, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, China.
authors.forename: Laijun
authors.initials: L
authors.lastname: Song
mesh_terms: D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D024243:HMGB1 Protein / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D024243:HMGB1 Protein
keywords: Autophagy; HMGB1; Schwann cells; neuroblastoma