At the nucleus of cancer - At the nucleus of cancer - how the nuclear envelope controls tumor progression - Review

Sep 23, 2026

Historically treated as downstream consequences of tumorigenesis, nuclear alterations have often been viewed as prognostic markers within a genome-centric framework. New evidence positions the nuclear envelope (NE) as an active regulator of tumor progression, especially in mediating cellular responses to mechanical forces. Remaining uncertainties persist regarding how NE components coordinate with cancer dynamics. This review synthesizes molecular and functional findings on NE composition, links them to malignant transformation, and highlights AI-assisted prediction and mechanotherapy.

LanguageEnglish

CategoryHealthcare

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Pages28

Reading Time1 h 11 min

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Abstract

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1 INTRODUCTION

DOI: 10.1002/mco2.70073 REVIEW At the nucleus of cancer: how the nuclear envelope controls tumor progression Francesca Paganelli1 Alberto M. Martelli1 Alessandro Poli2 Carla Palumbo3 Serena Truocchio1 Giovanna Lattanzi4, 5 Francesca Chiarini3 ,∗ 1 Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy 2 IFOM ETS-The AIRC Institute of Molecular Oncology, Milan, Italy 3 Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy 4 CNR Institute of Molecular Genetics“Luigi Luca Cavalli-Sforza”, Unit of Bologna, Bologna, Italy 5 IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy ∗ Correspondence Francesca Chiarini, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. Email: [francesca.chiarini@unimore.it](francesca.chiarini@unimore.it) Funding information Fondazione Cassa di Risparmio in Bologna, Grant/Award Number: 20024-(2022.0117); FAR Innovative Research UNIMORE Abstract Historically considered downstream effects of tumorigenesis—arising from changes in DNA content or chromatin organization—nuclear alterations have long been seen as mere prognostic markers within a genome-centric model of cancer. However, recent findings have placed the nuclear envelope (NE) at the forefront of tumor progression, highlighting its active role in mediating cellular responses to mechanical forces. Despite significant progress, the precise interplay between NE components and cancer progression remains under debate. In this review, we provide a comprehensive and up-to-date overview of how changes in NE composition affect nuclear mechanics and facilitate malignant transformation, grounded in the latest molecular and functional studies. We also review recent research that uses advanced technologies, including artificial intelligence, to predict malignancy risk and treatment outcomes by analyzing nuclear morphology. Finally, we discuss how progress in understanding nuclear mechanics has paved the way for mechanotherapy—a promising cancer treatment approach that exploits the mechanical differences between cancerous and healthy cells. Shifting the perspective on NE alterations from mere diagnostic markers to potential therapeutic targets, this review calls for further investigation into the evolving role of the NE in cancer, highlighting the potential for innovative strategies to transform conventional cancer therapies. KEYWORDS cancer, chromatin remodeling, lamins, mechanotransduction, nuclear envelope 1 INTRODUCTION It was the early 1700s when Anthony van Leeuwenhoek, often hailed as the father of optical microscopy, peered through his lens to reveal a central “clear area”within amphibian and avian erythrocytes.1 Building upon this groundwork, a century later, botanist Robert Brown introduced the concept of nucleated cells as fundamental structural units in plants and coined a term that would last in biology books to this day: the nucleus2 (Figure 1) . This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd. MedComm. 2025;6:e70073 . [https://doi.org/10.1002/mco2.70073](https://doi.org/10.1002/mco2.70073) [wileyonlinelibrary.com/journal/mco2](wileyonlinelibrary.com/journal/mco2) 1 of 28 PAGANELLI et al. FIGURE 1 Timeline of key milestones in the understanding of the composition and organization of the cell nucleus in healthy (lightblue boxes), cancer (light brown boxes), and laminopathic (green box) [cells. Created in BioRender.com. IF](cells. Created in BioRender.com. IF), intermediate filaments; LMNA, lamin A gene; NE, nuclear envelop

FAQs

Why has the nuclear envelope (NE) become central to understanding tumor progression?

Recent findings show the NE actively mediates cellular responses to mechanical forces, rather than only reflecting downstream consequences of DNA or chromatin changes.

What gap remains in current research on NE and cancer?

The precise interplay between NE components and cancer progression remains under debate.

How does the review connect NE research to emerging cancer treatments?

It discusses mechanotherapy, a promising approach that exploits mechanical differences between cancerous and healthy cells, enabled by advances in understanding nuclear mechanics.

Sep 23, 2026

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