Invited Talk

Cancer Cell Invasion – Plasticity of Biomechanics in Response to Energy Deprivation

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Metabolic stress is a frequent adverse event in tumors caused by mutations, malperfusion, hypoxia, and nutrition deficit. The resulting bioenergetic deprivation triggers signaling, mechanical and metabolic adaptation responses in tumor cells to secure survival and adjust migration activity. Recently, kinetic responses of cancer cells to energy deficit were identified, including a switch from energy-consuming collective to energy-efficient amoeboid migration and an enhanced capability for distant metastasis. The switch from collective to single-cell migration activation depended on activation of autophagy, which mediates rapid down-regulation of adherens junctions, followed by cell unjamming and individualization. In parallel, activation of calpain-2 limited integrin-mediated adhesion and mediated transition to low-adhesive, blebbing amoeboid migration mode along low- and mid-density, but not high-density ECM structures. Calpain-2 activity further supported increased tumor cell metastasis to the lungs. Understanding the biomechanics and energetic requirements of amoeboid and other dissemination strategies offers rationales for improving therapeutic targeting of metastatic cancer progression.