Canceromics studies unravel tumor’s glutamine addiction after metabolic reprogramming

Abstract

Metabolism is fundamental to cell survival, growth, and behavior. Tumor cells have an enhanced demand for nutrients which provide biosynthetic building blocks and cellular energy to sustain their proliferative status. Altered metabolism is a hallmark of cancer. The term metabolic reprogramming has been coined to describe the whole range of metabolic abnormalities accompanying tumorigenesis and metastasis. Increased glutamine uptake and glutaminolysis are key metabolic traits that have been consistently found on a wide range of human and experimental cancers. Glutaminase proteins control the first step in the glutaminolytic process: the conversion of glutamine to glutamate and ammonium ions. Glutaminase expression has been correlated with malignancy and growth rate on a great variety of tumors. Recent works are now starting to uncover the differential expression of glutaminase isoenzymes and their regulation by oncogenes and tumor suppressor genes. In parallel, glutaminase isoforms are attracting great interest as novel cancer chemotherapeutic targets. The focus of this chapter will highlight the role of glutamine addiction in tumor biology with particular emphasis on the interaction between the host and the tumor.