HMGB1 and cancer: In addition to its nuclear role, HMGB1 can be actively secreted by inflammatory cells and passively released from necrotic cells into the local microenvironment, acting as an extracellular signalling molecule that binds individual surface receptors, including the receptor for advanced glycation end products (RAGE) and Toll-like receptors (TLRs) –2, –4 and –9 during inflammation, cell migration, cell differentiation, and cancer metastasis13, 14.