Plasticity and Energy Adaptations in Cancer Cell Migration

Cancer cells that spread to other parts of the body to form metastases are really good at adapting to different environments. When moving, they need to make contacts with their surroundings and if they fail to do so, they die. For that reason, cells build up adhesive structures called focal adhesions. However, building and maintaining these connections takes a lot of energy. We propose that cancer cells can switch to an alternative, less energy-consuming method to stick around and move. Like efficient cars, cells employing energy-saving connections would cover greater distances with less fuel, which translates into more aggressive disease progression. Such energy-efficient connections are called endocytosis-related adhesions (ERAs). ERAs form when the outer layer of the cell bends inwards, which happens, for example, upon encountering a collagen fiber in the body. ERA are therefore employed to grab collagen fibers and help cells to move along the fibers the way a train moves on rails. Importantly, cancer cells move away from the tumor by migrating along the fibers present in the surrounding of tumors. If we take away the proteins needed to produce ERAs, the cells cannot follow collagen fibers anymore. This tells us that these alternative sticky connections could be required for cancer cells to move away and form metastases. We want to understand how cancer cells decide when to switch to these alternative connections. To do this, we will take advantage of CRISPR editing technology to generate cancer cell lines that are not able to use one of the two adhesion structures. We will then study how these cells move in the presence or absence of collagen fibers. Finally, we will measure how much energy do they burn to move in different environments. These experiments will allow us to identify the mechanism that makes cancer cells plastic and highly adaptable to different environments, providing new insights to combat cancer metastasis.