Illustration of PSC mechano-sensory driven regulation within a PDAC microenvironment. Under the effects of activating factors released from nearby cancer cells, local PSCs undergo phenotypic transition to a myofibroblast-like state, characterised by the secretion of vast amounts of ECM, providing a growth permissive environment for the neoplasm. Independently of PSC-cancer cell interactions, the generation of this highly stiff matrix mechanically activates local PSCs through mechanotransduction of the local microenvironment. This leads to increased matrix secretion and further PSC mechano-activation, resulting in the production of a positive mechanical activation feedback loop that produces a continually expanding region of fibrosis around the tumour. Such deposition leads to the generation of a stiffness gradient within the pancreas that is sensed by distant quiescent PSCs, causing them to undergo transition to an active state and begin durotactic migration towards the neoplasm, where upon they contribute to further matrix deposition. This accentuates the ever-growing area of fibrosis around the neoplasm through a vicious cycle of mechanically perturbed PSC activity.