Navigating the cancer cell nucleus: lamins at the interface of epigenetic regulation and tumorigenesis.

The spatial organization of the genome within the nucleus is a critical determinant of gene regulation, genome stability, and cellular identity. Disruption of nuclear architecture is increasingly recognized as a hallmark of cancer, contributing to transcriptional dysregulation, epigenetic reprogramming, and metastatic progression. Nuclear lamins, as key structural components of the nuclear envelope, play central roles in maintaining nuclear integrity and organizing chromatin through lamina-associated domains that are enriched in transcriptionally repressive states. Emerging pan-cancer studies reveal widespread dysregulation of lamin genes, with context-dependent roles in tumor suppression and oncogenesis. Alterations in lamin expression not only impact chromatin organization and gene expression but also influence nuclear mechanics, thereby facilitating invasion and metastasis. Increasing evidence suggests that epigenetic mechanisms tightly regulate lamin expression and function, linking chromatin state to nuclear structure. This interplay between epigenetic regulation and nuclear architecture drives large-scale genome reorganization and transcriptional plasticity in cancer. This review discusses the role of nuclear architecture in tumorigenesis, the contribution of lamins to chromatin organization, and the emerging epigenetic control of lamins in cancer progression and metastasis.