"Following ECM pathological remodelling, the aberrant activation of the mechanosensing apparatus contributes to the establishment and progression of age-related pathologies, like those affecting the cardiovascular system, and cancer. The mechanical turmoil associated with ECM remodeling is known to determine opposite consequences in rather different cell types, like cardiac and tumor cells: while cardiomyocytes in the heart are induced to hypertrophy by mechanical stress, cancer cells tend to proliferate and disseminate following similar stimuli.
Our group recently demonstrated how ECM pathological remodeling determines changes in the assembly of focal adhesions through the mechanical control of Hippo pathway downstream effector Yes Associated Protein (YAP) in breast cancer cells. The stained activation of this co-transcriptional activator has been independently associated to the growth and dissemination of many different tumor types.
Our group also described how YAP aberrant activation following pathological cardiac ECM remodelling plays a pivotal role in heart failure, by contributing to cardiac fibroblast activation and contractility.
In the context of the failing heart, we identified RNA binding proteins which are mechanosensitive and confer mRNA metabolism sensitivity to cardiac ECM mechanical turmoil and impinging on YAP alternative splicing. Finally, by employing bioengineered tools allowing the tight control of cell-matrix interaction and pluripotent stem cells, we also highlighted that mechanosensing is controlled in a stage-specific fashion and contributes critically to phenotype specification.
In conclusion, through a vast array of cellular models and bioengineered tools, we highlighted the pivotal role of mechanical cues in cell function and disease. "