Exploration of mechanical-stress promoted perturbation of the cell cycle in cancer cells

Mechanical forces represent important factors affecting (patho)physiology of cancer cells. Among the key mechanical stimuli encountered by tumor cells are: shear stress, various cell’s collisions and cellular compression induced by the flow of body fluids, as well as migration through interstitial spaces. Cancer cells are exposed to such forces particularly during the metastatic process when they become circulating in the blood. Little is known about the biological impact of these forces on the onset, progression and prognosis of the illness. In this project we propose to focus on mechanistic elucidation of cell cycle perturbation by which some cancer cells respond to the specific mechanical stimuli they experience upon entering the vascular system. We have developed a new approach mimicking the passive release of the mitotic cancer cells from the primary tumor followed by continuous mechanical stimuli resembling the vascular circulation forces. Our preliminary data show a G1-phase proliferation block featuring an intriguing molecular signature worthy of deeper mechanistic insight.