The protein complex AMPK is thought to suppress cancer, by slowing cellular metabolism, but it can also help some tumors grow.

But why? A new study says it has solved the mystery.

AMPK acts as a fuel gauge for the cell, overseeing energy input and output to keep the cell running smoothly. Similar to a car sensor flashing a low-gas signal or turning off a vehicle’s AC to save energy, AMPK slows down cell growth and changes the cell’s metabolism if the cell’s fuel (nutrients) is low.

Finding that late-stage cancers can trigger AMPK’s cellular recycling signal to cannibalize pieces of the cell, supplying large lung tumors with the nutrients they need to grow, the paper in Cell Metabolism suggests that blocking AMPK could stop the growth of advanced tumors in the most common type of lung cancer, non-small-cell lung cancer.

Credit: Genetic Analysis Reveals AMPK Is Required to Support Tumor Growth in Murine Kras-Dependent Lung Cancer Models, Eichner et al.

The team observed groups of mice with and without the AMPK fuel gauge to see how tumors developed. "We found that tumors grew much more slowly when AMPK was not present,” says Research Associate Lillian Eichner, the paper’s first author. “That means that AMPK is not always functioning as a tumor suppressor, as we originally thought.”

The team analyzed which genes in tumor cells from the same mouse models were being activated under various conditions. One gene that was particularly active was Tfe3, which is known to activate cellular recycling. It turned out that when tumors became large enough that cells in the middle were too far from easy access to nutrients, AMPK signaled Tfe3 to initiate recycling of cellular materials as nutrients—effectively cannibalizing pieces of the cell—for the tumor to use.