The expanding role of mTOR in cancer cell growth and proliferation

被引:154
作者
Cargnello, Marie [1 ]
Tcherkezian, Joseph [2 ]
Roux, Philippe P. [1 ,3 ]
机构
[1] Univ Montreal, IRIC, Montreal, PQ, Canada
[2] McGill Univ, Lab Therapeut Dev, Montreal, PQ, Canada
[3] Univ Montreal, Fac Med, Dept Pathol & Cell Biol, Montreal, PQ H3C 3J7, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
RIBOSOMAL-PROTEIN S6; TOP MESSENGER-RNAS; EUKARYOTIC TRANSLATION INITIATION; TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR COMPLEX; AMINO-ACID SUFFICIENCY; RAG GTPASES; SIGNAL INTEGRATION; MAMMALIAN PROTEIN; BINDING PROTEINS;
D O I
10.1093/mutage/geu045
中图分类号
Q3 [遗传学];
学科分类号
071007 [遗传学];
摘要
The mechanistic/mammalian target of rapamycin (mTOR) is a conserved protein kinase that controls several anabolic processes required for cell growth and proliferation. As such, mTOR has been implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes and neurodegeneration. As part of the mTOR complex 1 (mTORC1), mTOR regulates cell growth by promoting the biosynthesis of proteins, lipids and nucleic acids. Several mTORC1 substrates have been shown to regulate protein synthesis, including the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and the ribosomal S6 kinases (S6Ks) 1 and 2. In this work, we focus on the signalling pathways that lie both upstream and downstream of mTORC1, as well as their relevance to human pathologies. We further discuss pharmacological approaches that target mTOR and their applications for the treatment of cancer.
引用
收藏
页码:169 / 176
页数:8
相关论文
共 105 条
[1]
The 5' terminal oligopyrimidine-tract confers translational control on TOP mRNAs in a cell-type and sequence context-dependent manner [J].
Avni, D ;
Biberman, Y ;
Meyuhas, O .
NUCLEIC ACIDS RESEARCH, 1997, 25 (05) :995-1001
[2]
BANDI HR, 1993, J BIOL CHEM, V268, P4530
[3]
MOLECULAR-STRUCTURE OF A MAJOR INSULIN MITOGEN-ACTIVATED 70-KDA S6 PROTEIN-KINASE [J].
BANERJEE, P ;
AHMAD, MF ;
GROVE, JR ;
KOZLOSKY, C ;
PRICE, DJ ;
AVRUCH, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (21) :8550-8554
[4]
A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1 [J].
Bar-Peled, Liron ;
Chantranupong, Lynne ;
Cherniack, Andrew D. ;
Chen, Walter W. ;
Ottina, Kathleen A. ;
Grabiner, Brian C. ;
Spear, Eric D. ;
Carter, Scott L. ;
Meyerson, Matthew ;
Sabatini, David M. .
SCIENCE, 2013, 340 (6136) :1100-1106
[5]
Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels tomTORC1 [J].
Bar-Peled, Liron ;
Schweitzer, Lawrence D. ;
Zoncu, Roberto ;
Sabatini, David M. .
CELL, 2012, 150 (06) :1196-1208
[6]
Stimulation of de Novo Pyrimidine Synthesis by Growth Signaling Through mTOR and S6K1 [J].
Ben-Sahra, Issam ;
Howell, Jessica J. ;
Asara, John M. ;
Manning, Brendan D. .
SCIENCE, 2013, 339 (6125) :1323-1328
[7]
Rapamycin passes the torch: a new generation of mTOR inhibitors [J].
Benjamin, Don ;
Colombi, Marco ;
Moroni, Christoph ;
Hall, Michael N. .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (11) :868-880
[8]
Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis [J].
Bissler, John J. ;
McCormack, Francis X. ;
Young, Lisa R. ;
Elwing, Jean M. ;
Chuck, Gail ;
Leonard, Jennifer M. ;
Schmithorst, Vincent J. ;
Laor, Tal ;
Brody, Alan S. ;
Bean, Judy ;
Salisbury, Shelia ;
Franz, David N. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (02) :140-151
[9]
A MAMMALIAN PROTEIN TARGETED BY G1-ARRESTING RAPAMYCIN-RECEPTOR COMPLEX [J].
BROWN, EJ ;
ALBERS, MW ;
SHIN, TB ;
ICHIKAWA, K ;
KEITH, CT ;
LANE, WS ;
SCHREIBER, SL .
NATURE, 1994, 369 (6483) :756-758
[10]
A HIERARCHY OF ATP-CONSUMING PROCESSES IN MAMMALIAN-CELLS [J].
BUTTGEREIT, F ;
BRAND, MD .
BIOCHEMICAL JOURNAL, 1995, 312 :163-167