Super-resolution microscopy reveals the nanoscale cluster architecture of the DEK protein cancer biomarker

DEK protein, a key chromatin regulator, is strongly overexpressed in various forms of cancer. While con-ventional microscopy revealed DEK as uniformly distributed within the cell nucleus, advanced super-resolution techniques uncovered cluster-like structures. However, a comprehensive understanding of DEK's cellular distribution and its implications in cancer and cell growth remained elusive. To bridge this gap, we employed single-molecule localization microscopy (SMLM) to dissect DEK's nanoscale organization in both normal-like and aggressive breast cancer cell lines. Our investigation included characteristics such as localizations per cluster, cluster areas, and intra-cluster localization densities (ICLDs). We elucidated how cluster features align with different breast cell types and how chromatin decompaction influences DEK clusters in these contexts. Our results indicate that DEK's intra-cluster localization density and nano-organization remain preserved and not significantly influenced by protein overexpression or chromatin compaction changes. This study advances the understanding of DEK's role in cancer and under-scores its stable nanoscale behavior.