Tumor progression mediated by extracellular Hsp70 was further enhanced via a positive feedback loop stimulating a delayed activation of the JNK signaling cascade, leading to release of high mobility group protein B 1 (HMGB1) and upregulation of MMP-9 [171], both molecules playing a major role in tumor growth and invasion [172]. This evidence concerns the gene HMGB1 and neoplasm.