Role of lamins in cellular physiology and cancer.

Abstract

Lamins, which are crucial type V intermediate filament proteins found in the nuclear lamina, are essential for maintaining the stability and function of the nucleus in higher vertebrates. They are classified into A- and B-types, and their distinct expression patterns contribute to cellular survival, development, and functionality. Lamins emerged during the transition from open to closed mitosis, with their complexity increasing alongside organism evolution. Derived from the LMNA, LMNB1, and LMNB2 genes, lamins undergo alternative splicing to produce seven variants, influencing cellular processes such as stiffness, chromatin condensation, and cell cycle regulation. The lamin network interacts with the cytoskeleton via Linkers of the nucleoskeleton to the cytoskeleton (LINC) complexes, playing a critical role in cellular stability and mechanotransduction. Lamins also regulate active transport into and out of the nucleus, affecting nuclear integrity, positioning, DNA maintenance, and gene expression. Genetic mutations in lamin genes lead to laminopathies, highlighting their functional significance and organizational roles. Changes in lamin subtype composition within the nuclear lamina have significant implications for cancer development, impacting cellular stiffness, mobility, and the Epithelial-to-Mesenchymal Transition (EMT). Lamin A/C, in particular, plays multifaceted roles in cancer biology, influencing progression, metastasis, and therapy response through interactions with various proteins and pathways. Dysregulated lamin expression is commonly observed in cancers, suggesting their potential as diagnostic and prognostic markers. This chapter underscores the pivotal roles of lamins in nuclear architecture and cancer biology, emphasizing their impact on cellular functions and disease pathology. Understanding lamin behavior and regulation mechanisms holds promise for developing novel diagnostic tools and targeted therapies in cancer treatment.