Elucidating mechano-perception in cancer tissue

Early neoplastic transformation is associated with biomechanical modifications of the tumour tissue, resulting in increased tissue stiffening.

Aberrant deposition of collagen and extracellular matrix (ECM), leads to injurious mechanotransduction and activation of YAP/TAZ-transcriptional programs driving a self-reinforcing loop of exacerbated tissue remodelling.

Over time, the biomechanical changes induce tumour growth, metastatic spread and reprograming of cancer cells into self-renewing cancer stem cells with therapy-resistant properties.

This proposal aims to understand mechano-perception in breast and pancreas cancer tissue, with focus on identifying new regulators of cancer cell-intrinsic and extrinsic (ECM) modulators of mechanotransduction.

Our work demonstrate that CCM3 is a novel gatekeeper of mechanotransduction and YAP/TAZ signalling to take into consideration in cancer.

The proposal also aims at identifying new ways of reverting desmoplastic tissue to improve drug delivery and halt disease progression.

The use of inducible mouse models of breast and pancreatic cancer will identify spatial and temporal alterations in the cellular and acellular composition of the tumour tissue.

Finally, we will correlate the metastatic potential of circulating tumour cells from breast cancer patient based on their mechanical (viscoelastic) properties. In conclusion, the discovery of new modulators of mechano-perception has major clinical importance, not only in cancer.