Cancer cells require high amounts of energy to maintain rapid growth and proliferation and exhibit adaptive plasticity in their metabolism to meet these energy needs. Now, Jorge Moscat and colleagues show that loss of protein kinase Cζ (PKCζ) promotes the metabolic plasticity that cancer cells require (Cell 152, 599–611, 2013). The authors first knocked down PKCζ in SW480 cells and cultured these without medium changes, leading to nutrient exhaustion. Whereas control cells decreased in number, the proliferation of cells lacking PKCζ was not affected. Transcriptome analysis suggested that PKCζ-deficient cells used glutamine instead of glucose. Further experiments showed that serine-glycine biosynthesis was increased in cells using glutamine and that one of the functions of PKCζ is to redirect metabolism to a more efficient use of glutamine. To explore the metabolic effects of PKCζ loss in vivo, the authors implanted PKCζ-deficient cells in nude mice. They found that the growth rate of PKCζ-deficient xenografts was higher than that of controls. Analysis of several gene expression data sets from human colorectal tumors showed a loss of PKCζ expression. The authors conclude that PKCζ has an important role in metabolic plasticity in cancer cells, and potential treatments that counteract the well-known Warburg effect may be effective if PKCζ is activated.