Journal of Molecular Medicine

, Volume 94, Issue 8, pp 867–874 | Cite as

Pivotal role of high-mobility group box 1 (HMGB1) signaling pathways in glioma development and progression

  • Efthalia Angelopoulou
  • Christina Piperi
  • Christos Adamopoulos
  • Athanasios G. Papavassiliou


Human gliomas represent the most common type of intracranial tumors, with highest morbidity and mortality. They are characterized by excessive invasiveness and cell proliferation while their unclear boundaries predispose to tumor recurrence soon after conventional treatment. Elucidation of the molecular mechanisms implicated in their development and/or treatment resistance is highly demanded. The high-mobility group box 1 (HMGB1) protein, a highly conserved nuclear protein that functions as a chromatin-binding factor, facilitating nucleosome stabilization and regulating gene transcription, has been implicated in glioma formation and progression. Extracellular released HMGB1 binds to high-affinity receptors, including the receptor for advanced glycation end-products (RAGE) and toll-like receptor (TLR)-2, TLR-4, and TLR-9. Upon receptor binding, HMGB1 triggers the activation of key signaling pathways and immune responses, involved in the regulation of cell growth, differentiation, motility, and apoptosis. Based on the type of receptor and/or cell, HMGB1 is capable to promote oncogenesis or suppress tumor growth, thus affecting treatment efficacy. Herein, we discuss recent evidence implicating HMGB1 in glioma cell differentiation, proliferation, and metastasis with both clinical and prognostic significance. In addition, potential therapeutic approaches to target this protein in order to reduce chemoresistance of glioma cells are also addressed.


HMGB1 Gliomas Brain tumors RAGE TLRs Immunotherapy 



E. Angelopoulou is supported by a scholarship from “Alexander S. Onassis Public Benefit Foundation,” Greece.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Efthalia Angelopoulou
    • 1
  • Christina Piperi
    • 1
  • Christos Adamopoulos
    • 1
  • Athanasios G. Papavassiliou
    • 1
  1. 1.Department of Biological Chemistry, Medical SchoolNational and Kapodistrian University of AthensAthensGreece

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