Figure 2.

Cell cortical mechanics and its molecular drivers generate cell shape and morphogenesis, which collectively result in observed cell behaviors. The mechanical landscape and properties of cancer cells are significantly altered to drive metastasis and disease progression. Collectively, cytoskeletal components, regulators, and their resulting physical properties have been revealed as regulators of cancer cell growth and metastatic potential, TME interactions, stemness and differentiation, and metabolic reprogramming. Therefore, we propose the field of cancer cortical mechanics as a prospective area for exploration in disease prognosis, therapeutic targeting, elimination of therapeutic resistance, and prevention of clinical relapse. As a foundational system of cell behavior, cortical mechanics has the potential to concurrently address multiple drivers of disease progression, which is an ideal strategy for treating aggressive and unresponsive cancer types such as PDAC.