Project 459043

Cancer cells exhibit large differences in metabolism compared to healthy cells, particularly in how certain nutrients are used as fuel by cancer cells. Cancer cells not only have unique demands for specific nutrients, but are exposed to a unique environment within a tumor that provides limited access to many nutrients and oxygen. Through a poorly understood set of mechanism(s), cancer cells are able to adapt their metabolism to the nutrients in this otherwise restrictive environment, to not only survive, but thrive. Both healthy and cancer cells have a metabolic "fuel gauge" protein called AMPK that senses the availability of certain nutrients and then dictates the functions a cell is able to perform. How metabolic energy sensors such as AMPK are triggered to allow for this cancer cell nutrient and metabolism adaptation remains poorly understood, and understanding this is critical to reveal new weaknesses in cancer that can be used as targets for new therapies. In addition, cancer cell migration is a key component of cancer cell invasion and metastasis (cancer spreading). The process of cell migration is controlled by proteins known as integrins, and how metabolic sensors such as AMPK regulate integrin function is poorly understood. This research aims to understand how a novel set of signals triggered by AMPK may be a missing link in how cancer cells sense and adapt to otherwise restrictive nutrient conditions. Understanding how a cancer cell may uniquely use AMPK to adapt, thrive, and undergo metastasis may lead to the development of novel pharmacological drug targets for cancer therapy.