A liaison between mTOR signaling, ribosome biogenesis and cancer.
The ability to translate genetic information into functional proteins is considered a landmark in evolution. Ribosomes have evolved to take on this responsibility and, although there are some differences in their molecular make-up, both prokaryotes and eukaryotes share a common structural architecture and similar underlying mechanisms of protein synthesis. Understanding ribosome function and biogenesis has been the focus of extensive research since the early days of their discovery. In the last decade however, new and unexpected roles have emerged that place deregulated ribosome biogenesis and protein synthesis at the crossroads of pathological settings, particularly cancer, revealing a set of novel cellular checkpoints. Moreover, it is also becoming evident that mTOR signaling, which regulates an array of anabolic processes, including ribosome biogenesis, is often exploited by cancer cells to sustain proliferation through the upregulation of global protein synthesis. The use of pharmacological agents that interfere with ribosome biogenesis and mTOR signaling has proven to be an effective strategy to control cancer development clinically. Here we discuss the most recent findings concerning the underlying mechanisms by which mTOR signaling controls ribosome production and the potential impact of ribosome biogenesis in tumor development. This article is part of a Special Issue entitled: Translation and Cancer.
Laboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain. Electronic address: agentilella@idibell.cat.
Antonio
A
Gentilella
Laboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain; Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati Medical School, Cincinnati, 45267-0508 OH, USA.
Sara C
SC
Kozma
Laboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain; Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati Medical School, Cincinnati, 45267-0508 OH, USA. Electronic address: gthomas@idibell.cat.
George
G
Thomas
D000818:Animals; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D009363:Neoplasm Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
Cancer; Ribosomal protein; Ribosome biogenesis; mTOR