Decoding Tumor Mechanobiology: Regulation, Signalling, and Translational Impact

The field of molecular cancer mechanobiology focuses on the ways in which cells sense and respond to mechanical cues within the tumor microenvironment. Mechanical properties such as extracellular matrix (ECM) stiffness, geometry, and dynamic remodeling play pivotal roles in regulating tumor initiation, progression, and treatment response. An expanding body of evidence highlights that these physical cues activate a complex web of mechanotransduction pathways, involving focal adhesion signaling, cytoskeletal contractility, mechanosensitive membrane complexes, and nuclear mechanotransduction. Despite advances in understanding these mechanisms, crucial questions remain about how anti-cancer therapies interact with mechanical microenvironments and the subsequent effects on resistance, relapse, and cell plasticity.Recent studies reveal that treatments like ionizing radiation, chemotherapy, and immunotherapy can modulate the tumor’s mechanical landscape, impacting mechanoresponsive signaling and transcriptional states in a manner dependent on ECM properties. For example, altered ECM stiffness may change how cancer cells process therapeutic signals and activate survival pathways, while treatment-driven matrix remodeling can either support or hinder malignant behaviors. While integrative modeling and advanced experiments have begun to unravel the cross-talk between treatment modalities and mechanical signals, our knowledge of the molecular underpinnings and context-specific pathway rewiring remains incomplete. Ongoing debates revolve around the precise identification of mechanosensitive molecular hubs, the reversibility of treatment-induced changes, and their implications for clinical intervention.This Research Topic aims to gather mechanistic and integrative investigations that demystify how physical forces are transduced into biochemical and transcriptional programs in cancer, and how these understandings can inform diagnostics and treatment strategies. Contributions should explore the deep molecular basis of mechanotransduction—such as adhesome dynamics, mechanosensitive signaling modules, mechano-epigenetics, and nuclear–chromatin coupling—supported by rigorous experimental validation and, if appropriate, theoretical or computational modeling. The ultimate objective is to encourage approaches that reveal how disruptions and interventions in these pathways may be harnessed for improved cancer management.To gather further insights in molecular cancer mechanobiology, with a focus on the interplay between mechanical cues and therapeutic outcomes, we welcome articles addressing, but not limited to, the following themes:- Mechanotransduction at focal adhesions and within the adhesome- Cytoskeletal contractility and mechanochemical feedback regulation- Nuclear mechanotransduction, chromatin remodeling, and mechano-epigenetics- Tumor microenvironment mechanics and ECM remodeling processes- Interactions between mechanical microenvironments and anti-cancer therapies- Mechanobiology-driven diagnostics, biomarkers, and mechanosignatures- Computational and multiscale modeling validated by experimental studies- Prospective mechano-therapeutic targets and combination strategies Topic editors: Valeria Panzetta, Carlo F. Natale, Paulina Nastaly Source: https://www.frontiersin.org/research-topics/77158/decoding-tumor-mechanobiology-regulation-signalling-and-translational-impact