Glutamine dependence and PIK3CA mutations in colon-rectal cancer cells: ATF4 enters the stage

Capacity to reprogram the metabolic activities exhibited by cancer cells distinguishes tumors from normal tissues supporting their unregulated growth. While alterations in glucose metabolism were the first cancer-related metabolic anomalies to be detected and extensively investigated, in the last years an increasing number of studies has progressively unveiled the role that the amino acid glutamine plays in an enlarging group of human tumors. Glutamine, as a potential donor of either carbon or nitrogen, plays several metabolic roles. Some of these are ubiquitous, others strictly tissue specific (1). In selected cancer types, glutamine is avidly transported from the extracellular compartment, and its metabolism is up-regulated to provide energy production and sustain biosynthetic aims. Cancers that exhibit particularly high requirements for glutamine are named glutamine-addicted (2). A variety of oncogenes and tumor suppressor genes impact glutamine metabolism in cancer cells (1) including Myc overexpression (1), p53 (3), Rb tumor suppressor (4) and Von Hippel-Lindau (VHL) suppressor through hypoxia-inducible factor (HIF)-1 (5). Nevertheless, the mechanism by which many cancer cells become dependent on glutamine is still under investigation.