Although the mechanism of extracellular HMGB1 secretion upon Ang II-induced cardiomyocyte hypertrophy is poorly understood, Oh et al. demonstrated that classical PKC, not ERK or NF-κB, can phosphorylate HMGB1, resulting in extracellular HMGB1 secretion from LPS-stimulated Raw264.7 cells, and An et al. showed PKC-induced phosphorylation and secretion of HMGB1 using a bone cancer pain model [45,46]. This evidence concerns the gene HMGB1 and bone neoplasm.