# Nuclear destabilisation – a possible genesis of cancer?

## TL;DR

This paper suggests that cancer may originate from mechanical instability in the cell nucleus, leading to genetic and epigenetic changes.

## Contribution

The paper proposes nuclear destabilization as a novel unifying mechanism for cancer initiation and progression.

## Key findings

- Cell mechanical properties are tightly regulated and may be central to cancer formation.
- Nuclear destabilization, particularly in the nucleosome, could lead to chromatin dysfunction and genetic dysregulation.
- Mechanical changes in the nucleus may explain the variability and heterogeneity of cancer genetics.

## Abstract

This review examines the increasingly prominent role of mechanics within cancer formation and progression. The extremely varied and contradictory genetic landscape of cancer is in stark contrast to the seemingly universal mechanical characteristics of cancer cells and their tumour microenvironment, and mechanics may be a principal unifying trait of this disease. The tight regulation of innate cell mechanical properties raises the possibility that destabilisation of the cell drives tumour formation in an attempt to restore cell mechanical homeostasis. With losses in cell stiffness more pronounced at the cell nucleus, we hypothesise that destabilisation occurs within the nucleus, likely within the nucleosome. Beyond the mechanical properties of the cell, this compromise to the chromatin structure holds significant repercussions for both genetic and epigenetic regulation, providing scope for significant genetic dysregulation and mutation. However, the nature of such genetic events will be dependent upon the region of mechanical destabilisation; thus, introducing greater variability and heterogeneity to genetic changes. We conclude with the hypothesis that cancer has a mechanical genesis, in which cell nuclear destabilisation functions as the enabling hallmark of cancer. It is theorised that both genetic and structural dysfunction stem from this nuclear destabilisation, driving disease pathology and progression.