Mechanical load inhibits cancer growth in mouse and human hearts

• 成果类型: Article
• 署名作者: Ciucci, Giulio; Lorizio, Daniela; Bartoloni, Nicoletta; Budini, Mauricio; Colliva, Andrea; Vodret, Simone; Nguyen, Anh-Vu; Ciacci, Lorenzo; Texler, Bernhard; Cardini, Benno; Oberhuber, Rupert; Bindelli, Sofia; Del Giudice, Ilaria Luciana Carlotta; Vuerich, Roman; Riccitelli, Francesco; Zago, Elena; Finsberg, Henrik Nicolay; Chiesa, Mattia; Perrucci, Gianluca Lorenzo; Bussani, Rossana; Silvestri, Furio; Maglione, Manuel; Dellino, Gaetano Ivan; Sinagra, Gianfranco; Giacca, Mauro; Eschenhagen, Thomas; Golino, Paolo; Pompilio, Giulio; Pelicci, Pier Giuseppe; Andolfi, Laura; Pinamonti, Maurizio; Dal Ferro, Matteo; Wall, Samuel; Loffredo, Francesco S.; Zacchigna, Serena
• 署名单位: International Center for Genetic Engineering & Biotechnology (ICGEB); IRCCS Centro Cardiologico Monzino; University of Trieste; Medical University of Innsbruck; IRCCS European Institute of Oncology (IEO); University of Milan; University of London; King's College London; University of London; King's College London; University of Hamburg; University Medical Center Hamburg-Eppendorf; German Centre for Cardiovascular Research; Universita della Campania Vanvitelli; University of Milan; Consiglio Nazionale delle Ricerche (CNR); Istituto Officina dei Materiali (IOM-CNR)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ads9412
• 发表日期: 2026-04-23
• 页码: eads9412
• 关键词: PROLIFERATION; metastasis

摘要

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.