Fibroblast pyruvate carboxylase is required for collagen production in the tumor microenvironment

The aberrant production of collagen by fibroblasts is a hallmark of many solid tumors and can influence cancer progression. How fibroblasts produce collagen within tumor microenvironments which are nutrient-poor is not understood. Here, we show that pyruvate carboxylase (PC) activity increases in fibroblasts cultured in a low glutamine environment, and that PC is required for collagen production by tumor-associated fibroblasts in vivo. Overall design: RNA-sequencing of NIH-3T3 cells expressing a control sgRNA (R26 sg1), PC sg2 or PC sg5, cultured for 48h in DMEM containing 0.2 mM L-glutamine