HMGB1-its role in tumor progression and anticancer therapy

HMGB1 is an evolutionarily conserved protein with a wide spectrum of action. Its main receptors are RAGE and TLR found on the surface of immune system cells as well as endothelial cells. Although signaling pathways for both receptor groups are different, ultimately they both activate NF kappa B transcription factor which, in turn, activates genes encoding adhesion proteins, proinflammatory cytokines and proangiogenic factors. Inside cells, HMGB1 is found mainly in the cell nucleus, where it participates in replication, recombination, transcription and DNA repair processes. Following release into the extracellular space, HMGB1 becomes a proinflammatory cytokine which stimulates formation of new blood microvessels, enhances cell migration, activates the inflammatory condition and affects cell proliferation. HMGB1 protein also takes part in regeneration of damaged tissues and stimulates autophagy. HMGB1 plays a potential role in anticancer therapy. Increased amounts of HMGB1 in cancer cells and elevated levels in the bloodstream are noted among patients afflicted with various cancers. HMGB1 protects cells from apoptosis, as it affects telomere stability. HMGB1 also stimulates a number of proteins involved in proliferation of cancer cells and inhibits signals that control cell growth. Ability to arrest HMGB1 release from cells or to inhibit its activity appears to be a promising therapeutic approach. At present, several inhibitors of HMGB1 are known and can be used in anticancer therapy.