Effect of mechanical forces on cellular response to radiation.
Effect of mechanical forces on cellular response to radiation.
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DOI：
10.1016/j.radonc.2022.10.006
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发表时间：
2022-11
影响因子：
5.7
通讯作者：
Zenhausern, Frederic
中科院分区：
文献类型：
--
作者：
Lacombe, Jerome;Zenhausern, Frederic
虽然细胞相互作用和生化信号已经被研究了很长时间，并在细胞的命运中发挥了重要作用，但现在也很明显，持续施加于细胞微环境中的机械力对组织稳态同样重要。机械信号正在成为细胞药物反应的关键调节因子，我们的目的是在这篇综述中证明，这种效应也应该被认为是细胞对辐射反应的重要因素。为了探索辐射反应的机制生物学，我们综述了主要的机制受体和转导器，包括整合素介导的粘附、YAP/TAZ通路、Wnt/β-catenin信号传导、离子通道和G蛋白偶联受体，并揭示了它们在细胞辐射敏感性调节中的作用。然后，我们讨论了目前研究的机械应力，包括细胞外基质刚度，剪切应力和机械应变，对癌症和正常细胞辐射反应的直接影响，并通过初步结果表明，这种应力可以有效地改变辐照后细胞的反应。然而，我们也强调了这些研究的局限性，并强调了一些相互矛盾的数据，表明机械信号的影响可能涉及复杂的相互作用和潜在的串扰，许多细胞过程也受到辐射的影响。总的来说，机械力改变了辐射反应，尽管需要进一步的研究来深入了解潜在的机制，但这些影响在辐射研究中不应被忽视，因为它们可以为预测放射敏感性或了解放射治疗耐药性提供新的基础知识。
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.
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影响因子：
7.7
作者：
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