title: Signaling to the ribosome in cancer--It is more than just mTORC1.
abstract: It is becoming increasingly clear that dysregulation of protein synthesis contributes to a range of diseases characterized by tissue overgrowth. These include arterial stenosis, cardiac hypertrophy, hamartomas, and cancer. The central hub for the regulation of protein synthesis is the ribosome, where the key signaling pathways downstream of RAS, MYC, and phosphatidylinositol-3-kinase (PI3K) converge to confer exquisite, coordinated control of ribosome synthesis and function. Such cooperation ensures strict regulation of protein synthesis rates and cell growth. This review will focus on the role the PI3K/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway plays in regulating ribosome function during both health and disease, its interaction with the other key growth regulatory pathways activated by RAS and MYC, and the therapeutic potential for targeting this network.
authors.affiliation: Growth Control and Differentiation Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, VIC, Australia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Hannan
authors.forename: Elaine
authors.initials: E
authors.lastname: Sanij
authors.forename: Nadine
authors.initials: N
authors.lastname: Hein
authors.forename: Ross D
authors.initials: RD
authors.lastname: Hannan
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pearson
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000737:chemistry; D058570:TOR Serine-Threonine Kinases; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt; D016271:Proto-Oncogene Proteins c-myc; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D018631:ras Proteins