Mechanical load inhibits cancer growth in mouse and human hearts

Science 2026

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Authors: Giulio Ciucci, Daniela Lorizio, Nicoletta Bartoloni, Mauricio Budini, Andrea Colliva, Simone Vodret, Anh-Vu Nguyen, Lorenzo Ciacci, Bernhard Texler, Benno Cardini, Rupert Oberhuber, Sofia Bindelli
+23 more Ilaria Luciana Carlotta Del Giudice, Roman Vuerich, Francesco Riccitelli, Elena Zago, Henrik Nicolay Finsberg, Mattia Chiesa, Gianluca Lorenzo Perrucci, Rossana Bussani, Furio Silvestri, Manuel Maglione, Gaetano Ivan Dellino, G Sinagra, Mauro Giacca, Thomas Eschenhagen, Paolo Golino, G Pompilio, Pier Giuseppe Pelicci, Laura Andolfi, Maurizio Pinamonti, Matteo Dal Ferro, Samuel Wall, Francesco S. Loffredo, Serena Zacchigna
DOI: 10.1126/science.ads9412
Cited by: 15
References: 71

Abstract

The heart rarely develops cancer, and, at the same time, it lacks regenerative capacity, as cardiomyocytes stop proliferating after birth. This suggests that mechanisms limiting cardiac regeneration may also protect against cancer. In this work, we investigated the role of mechanical load and used in vivo cancer models and ex vivo engineered heart tissues to show that mechanical load reduces cancer cell proliferation in the myocardium. Spatial transcriptomics of human cardiac metastases revealed decreased histone methylation and chromatin compaction. These changes affect chromatin accessibility at proliferation-related loci, with Nesprin-2 identified as a key mechanosensor. Our results uncover how mechanical forces protect the heart from cancer and suggest potential strategies for cancer therapy based on mechanical stimulation.

Fields of Study & Subjects

Congenital heart defects research Cardiomyopathy and Myosin Studies Cardiac Fibrosis and Remodeling

Publication details

Journal / source
Science
Publisher
American Association for the Advancement of Science (AAAS)
Volume
392
Issue
6796
Pages
eads9412–eads9412
Publication date
23 April 2026
Language
EN