The Extracellular Matrix Contributes to Mechanotransduction in Uterine Fibroids

Figure 2

Elements of mechanical signaling. A simplified pathway of mechanical signaling in cells is depicted. As the cell cytoskeleton contracts (a process called cell contractility) and ECM accumulates in the cell microenvironment, integrin activation occurs leading to activation of Rho (as discussed in [1]). Rho in turn activates ROCK leading to activation of ras. In fibroid cells obtained either at the time of hysterectomy or myomectomy, RhoA activity is attenuated. This adaptation of the fibroid cell is not ROCK dependent (as discussed in [2]). These findings suggest that fibroid cells in symptomatic tumors where treatment was needed are fundamentally adapted to their stiff microenvironment and thus become insensitive to moderate mechanical cues. It is not certain when in the natural history of fibroid development that this adaptive response to mechanotransduction occurs. Nevertheless, mechanical sensing does occur in fibroid cells.