Jan Lammerding, Project Leader
Cell invasion from the primary tumor into surrounding tissues is a crucial step of the metastatic cascade, which is responsible for the vast majority of cancer deaths. We propose that invading cancer cells must expend significant energy to penetrate through tight interstitial spaces, and adopt migration modes that minimize metabolic cost. The research in this project will address how the interaction between invading cells and the physical microenvironment determine energy consumption; how physical factors intrinsic to the cell, particularly nuclear deformability and the physical properties of the cell surface, modulate metabolic cost and migration efficiency; and how metabolic reprogramming in cancer cells affects migration efficiency by fueling biosynthetic pathways that alter cellular mechanics. The experimental work will be complemented by modeling of cancer cell metabolism and physical interaction with the microenvironment, with the objective to predict outcomes of therapeutic metabolic interventions and to identify strategies to counter adaptive responses.