PMID- 38474373
OWN - NLM
STAT- MEDLINE
DCOM- 20240314
LR  - 20240315
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 13
IP  - 5
DP  - 2024 Feb 27
TI  - Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and 
      Therapeutic Targets.
LID - 10.3390/cells13050409 [doi]
LID - 409
AB  - The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that 
      functions via its discrete binding partners to form two multiprotein complexes, 
      mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which 
      regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt 
      and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive 
      to neurotransmitter signaling. mTORC2, which is modulated by growth factor 
      signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR 
      regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR 
      activation is involved in multistep tumorigenesis in a variety of cancers, 
      thereby suggesting that the inhibition of mTOR may have therapeutic potential. 
      Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through 
      an allosteric mechanism that only suppresses mTORC1, albeit incompletely. 
      ATP-catalytic binding site inhibitors are designed to inhibit both complexes. 
      This review describes the regulation of mTOR and the targeting of its complexes 
      in the treatment of cancers, such as glioblastoma, and their stem cells.
FAU - Jhanwar-Uniyal, Meena
AU  - Jhanwar-Uniyal M
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Zeller, Sabrina L
AU  - Zeller SL
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Spirollari, Eris
AU  - Spirollari E
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Das, Mohan
AU  - Das M
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Hanft, Simon J
AU  - Hanft SJ
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Gandhi, Chirag D
AU  - Gandhi CD
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
LA  - eng
GR  - NA/Advanced Research Foundation/
PT  - Journal Article
PT  - Review
DEP - 20240227
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - *Glioblastoma/metabolism
MH  - Intercellular Signaling Peptides and Proteins/therapeutic use
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - *Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - *Neoplastic Stem Cells/metabolism
PMC - PMC10930964
OTO - NOTNLM
OT  - 4E-BP1
OT  - GBM
OT  - S6K
OT  - mTOR
OT  - mTORC1
OT  - mTORC2
COIS- The authors declare no conflicts of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2024/03/13 06:47
MHDA- 2024/03/14 06:47
PMCR- 2024/02/27
CRDT- 2024/03/13 01:25
PHST- 2024/01/16 00:00 [received]
PHST- 2024/02/14 00:00 [revised]
PHST- 2024/02/22 00:00 [accepted]
PHST- 2024/03/14 06:47 [medline]
PHST- 2024/03/13 06:47 [pubmed]
PHST- 2024/03/13 01:25 [entrez]
PHST- 2024/02/27 00:00 [pmc-release]
AID - cells13050409 [pii]
AID - cells-13-00409 [pii]
AID - 10.3390/cells13050409 [doi]
PST - epublish
SO  - Cells. 2024 Feb 27;13(5):409. doi: 10.3390/cells13050409.