Mechanisms of nuclear size regulation in model systems and cancer.

Changes in nuclear size have long been used by cytopathologists as an important parameter to diagnose, stage, and prognose many cancers. Mechanisms underlying these changes and functional links between nuclear size and malignancy are largely unknown. Understanding mechanisms of nuclear size regulation and the physiological significance of proper nuclear size control will inform the interplay between altered nuclear size and oncogenesis. In this chapter we review what is known about molecular mechanisms of nuclear size control based on research in model experimental systems including yeast, Xenopus, Tetrahymena, Drosophila, plants, mice, and mammalian cell culture. We discuss how nuclear size is influenced by DNA ploidy, nuclear structural components, cytoplasmic factors and nucleocytoplasmic transport, the cytoskeleton, and the extracellular matrix. Based on these mechanistic insights, we speculate about how nuclear size might impact cell physiology and whether altered nuclear size could contribute to cancer development and progression. We end with some outstanding questions about mechanisms and functions of nuclear size regulation.