Effect of mechanical forces on cellular response to radiation. (November 2022)

• Record Type: Journal Article
• Authors: Lacombe, Jerome; Zenhausern, Frederic
• Is Part Of: Radiotherapy and oncology. Volume 176(2022)
• Page Start: 187
• Page End: 198
• Publication Date: 2022-11
• Subjects: Radiation -- Mechanical forces -- Stiffness -- Shear stress -- Mechanotransduction -- Mechanoreceptors; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2022.10.006
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: Classical mechanotransducers are involved in the modulation of radiation response. Mechanical stress affects cellular radiosensitivity. Mechanisms involved in mechanical-mediated radiation response are unclear. Novel bioengineered platform technologies allow integration of mechanical forces. Radiation community should integrate mechanical forces as important radiomodulator. Abstract: While the cellular interactions and biochemical signaling has been investigated for long and showed to play a major role in the cell's fate, it is now also evident that mechanical forces continuously applied to the cells in their microenvironment are as important for tissue homeostasis. Mechanical cues are emerging as key regulators of cellular drug response and we aimed to demonstrate in this review that such effects should also be considered vital for the cellular response to radiation. In order to explore the mechanobiology of the radiation response, we reviewed the main mechanoreceptors and transducers, including integrin-mediated adhesion, YAP/TAZ pathways, Wnt/β-catenin signaling, ion channels and G protein-coupled receptors and showed their implication in the modulation of cellular radiosensitivity. We then discussed the current studies that investigated a direct effect of mechanical stress, including extracellular matrix stiffness, shear stress and mechanical strain, on radiation response of cancer and normal cells and showed through preliminary results that such stress effectively can alter cell response after irradiation. However, we also highlighted the limitations of these studies and emphasized some of the contradictory data, demonstrating that the effect of mechanical cues could involve complex interactions and potential crosstalk with numerous cellular processes also affected by irradiation. Overall, mechanical forces alter radiation response and although additional studies are required to deeply understand the underlying mechanisms, these effects should not be neglected in radiation research as they could reveal new fundamental knowledge for predicting radiosensitivity or understanding resistance to radiotherapy.