Cancer progression is dependent on heightened mechanical adaptation, both for the cells' ability to change shape and to interact with varying mechanical environments. This type of adaptation is dependent on mechanoresponsive proteins that sense and respond to mechanical stress, as well as their regulators. Mechanoresponsive proteins are part of the mechanobiome, which is the larger network that constitutes the cell's mechanical systems that are also highly integrated with many other cellular systems, such as gene expression, metabolism, and signaling. Despite the altered expression patterns of key mechanobiome proteins across many different cancer types, pharmaceutical targeting of these proteins has been overlooked. Here we review the biochemistry of key mechanoresponsive proteins, specifically nonmuscle myosin II, α-actinins, and filamins, as well as the partnering proteins 14-3-3 and CLP36. We also examined a wide range of data sets to assess how gene and protein expression levels of these proteins are altered across many different cancer types. Finally, we determined the potential of targeting these proteins to mitigate invasion or metastasis and suggest that the mechanobiome is a goldmine of opportunity for anti-cancer drug discovery and development.

中文翻译：

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Mechanobiome：癌症治疗的金矿

癌症进展依赖于增强的机械适应能力，包括细胞改变形状和与不同机械环境相互作用的能力。这种类型的适应依赖于感知和响应机械应力的机械响应蛋白，以及它们的调节器。机械响应蛋白是机械生物群的一部分，机械生物群是构成细胞机械系统的更大网络，这些机械系统也与许多其他细胞系统高度整合，例如基因表达、代谢和信号传导。尽管许多不同癌症类型的关键机械生物组蛋白的表达模式发生了改变，但这些蛋白的药物靶向作用却被忽视了。在这里，我们回顾了关键机械反应蛋白的生物化学，特别是非肌肉肌球蛋白 II、α-肌动蛋白、和细丝蛋白，以及配对蛋白 14-3-3 和 CLP36。我们还检查了广泛的数据集，以评估这些蛋白质的基因和蛋白质表达水平如何在许多不同的癌症类型中发生改变。最后，我们确定了靶向这些蛋白质以减轻侵袭或转移的潜力，并表明机械生物组是抗癌药物发现和开发的金矿。