Abstract
H11/HspB8 is a functionally distinct small heat shock protein. It causes growth arrest in melanocytes, associated with the inhibition of Cyclin E/Cdk2 and β-catenin phosphorylation at the transcriptional activity site Ser(552) and is silenced through DNA methylation in 27/35 (77%) melanoma tissues/early cultures. 5-Aza-2'-deoxycytidine (Aza-C) induces melanoma cell death correlated with the levels of H11/HspB8 DNA methylation (p < .001). In line with low/moderate H11/HspB8 methylation, PI3-K inhibition increases Aza-C-induced cell death. Aza-C inhibits the growth of melanoma xenografts related to the levels of H11/HspB8 methylation, and a nonmethylated/non-TAK1 binding H11/HspB8 mutant confers Aza-C resistance. H11/HspB8 is a potential molecular marker for demethylation therapies.