Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that prosenescence therapies could be employed against SWI/SNF-mutated cancers.
SWI/SNF chromatin remodeling complex may be an attractive candidate for being the "second hit" in RCCs and may play an important role during tumor progression.
Similar to other chromatin remodellers, such as SWI/SNF and Polycomb complexes, NuRD has also been implicated in the regulation of transcriptional events that are integral to oncogenesis and cancer progression.
Collectively, these data implicate loss of SWI/SNF-mediated transcriptional activation as a novel mechanism to increase DNA methylation in cancer cells and provide insight into the mechanisms underlying aberrant gene induction and repression during tumor progression.