Enlarged Cancer Cell Nuclei May Play a Protective Role Against Metastasis

In tissue biopsies, cancer cells often display enlarged nuclei, which store the cell's genetic information. Traditionally, this characteristic was considered an indicator of tumor progression and severity. However, recent research challenges this assumption by revealing a more nuanced role of nuclear hypertrophy.

A study conducted by a team at KAIST led by Professor Joon Kim investigated the underlying causes and implications of enlarged nuclei in cancer cells. The findings suggest that nuclear hypertrophy is not necessarily a sign of increased malignancy. Instead, it appears to be a temporary cellular response to replication stress—a condition where the copying of DNA during cell division is hindered, often due to errors orBurdenSignal signals within the cell.

The research demonstrated that DNA replication stress causes the actin protein within the nucleus to polymerize and aggregate. This process results in an increase in nuclear size but also appears to suppress the cancer cells' ability to metastasize. Multiple analyses, including gene function screening, transcriptome analysis, and 3D genome structuring, confirmed that nuclear hypertrophy influences changes in DNA configuration and chromatin topology, ultimately reducing cellular motility and metastatic potential.

Notably, experiments using mouse xenograft models showed that cancer cells with enlarged nuclei exhibited decreased motility and metastatic behavior. Professor Kim explained that these findings highlight nuclear hypertrophy as a response mechanism rather than a malignant trait, opening new avenues for diagnosis and treatment. The research suggests that monitoring nuclear size changes could serve as an indicator for cancer diagnosis and metastasis prediction, rather than an outright marker of severity.

The study, published in the Proceedings of the National Academy of Sciences, underscores the importance of understanding cellular stress responses in cancer. It opens the possibility of developing therapeutic strategies that exploit nuclear structural changes to inhibit metastasis, ultimately contributing to more effective and targeted cancer treatments.

Source: https://medicalxpress.com/news/2025-09-enlarged-cancer-cell-nuclei-limit.html