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 anticancer drug discovery and development.