The nexus of nuclear envelope dynamics, circular economy and cancer cell pathophysiology

Abstract

The nuclear envelope (NE) is a critical component in maintaining the function and structure of the eukaryotic nucleus. The NE and lamina are disassembled during each cell cycle to enable an open mitosis. Nuclear architecture construction and deconstruction is a prime example of a circular economy, as it fulfills a highly efficient recycling program bound to continuous assessment of the quality and functionality of the building blocks. Alterations in the nuclear dynamics and lamina structure have emerged as important contributors to both oncogenic transformation and cancer progression. However, the knowledge of the NE breakdown and reassembly is still limited to a fraction of participating proteins and complexes. As cancer cells contain highly diverse nuclei in terms of DNA content, but also in terms of nuclear number, size, and shape, it is of great interest to understand the intricate relationship between these nuclear features in cancer cell pathophysiology. In this review, we provide insights into how those NE dynamics are regulated, and how lamina destabilization processes may alter the NE circular economy. Moreover, we expand the knowledge of the lamina-associated domain region by using strategic algorithms, including Artificial Intelligence, to infer protein associations, assess their function and location, and predict cancer-type specificity with implications for the future of cancer diagnosis, prognosis and treatment. Using this approach we identified NUP98 and MECP2 as potential proteins that exhibit upregulation in Acute Myeloid Leukemia (LAML) patients with implications for early diagnosis.