B-cell lymphomas are the most frequent human immune system cancers. Epigenetic changes, such as DNA hypermethylation, may promote B-cell transformation by silencing tumor suppressor genes.
Expression levels SPAK, a protein that regulates cellular stress responses, are reduced during cancer progression. Using a mouse model of B-cell malignancies and human B-cell lymphoma tissue samples, Balatoni et al report that SPAK expression is inhibited in B-cell tumors due in part to hypermethylation. Decreased SPAK expression protected B cells from environmental stressors that would induce cell death in non-cancerous cells. This SPAK-silenced protection may therefore be responsible for survival and metastatic progression in DNA-damaged B cells.
Dr. Teitell and colleagues suggest "that SPAK silencing in B-cell lymphomas promotes cancer progression by crippling genotoxic stress signaling to impair caspase activation. These results likely generalize to breast, prostate, and possibly other cancers beyond B lymphoma and uncover a novel role for SPAK in controlling the DNA damage response, highlighting a protective cell death mechanism that is disabled during the progression of cancer. SPAK expression or repression may also help indicate those patient tumors that should or should not receive genotoxic therapies as the development of personalized medicine pushes ahead."
By American Journal of Pathology