Signal Integration and Cellular Decisions

We are studying how multiple nutrient signaling pathways are integrated into discrete decisions.

To allow for uncontrolled growth, cancer cells have to bypass nutrient checkpoints and alter their metabolism without compromising basic cellular functions. In mammalian cells, the RAS/PKA, TOR, and AMPK pathways are important for this decision.

Cancer can be caused by any set of mutations that shifts the steady-state of these pathways from quiescence to proliferation, but we have yet to understand the dynamics of the mechanisms that govern this shift. To fully understand cancer, we need to understand how metabolism is integrated with growth and proliferation.

However, the complexity of the system makes it hard to approach through conventional methods. To overcome these difficulties, we will first address this question in a tractable model system with a well-defined decision downstream of this signaling nexus—yeast meiosis—and later in mammalian systems.  

Cancer cells promote proliferation by altering the integration of input signals (blue) and nutrients (orange).