PMID- 30347859
OWN - NLM
STAT- MEDLINE
DCOM- 20190129
LR  - 20220924
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 10
DP  - 2018 Oct 21
TI  - mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression.
LID - 10.3390/ijms19103267 [doi]
LID - 3267
AB  - Recent advancement in the field of molecular cancer research has clearly revealed 
      that abnormality of oncogenes or tumor suppressor genes causes tumor progression 
      thorough the promotion of intracellular metabolism. Metabolic reprogramming is 
      one of the strategies for cancer cells to ensure their survival by enabling 
      cancer cells to obtain the macromolecular precursors and energy needed for the 
      rapid growth. However, an orchestration of appropriate metabolic reactions for 
      the cancer cell survival requires the precise mechanism to sense and harness the 
      nutrient in the microenvironment. Mammalian/mechanistic target of rapamycin 
      (mTOR) complexes are known downstream effectors of many cancer-causing mutations, 
      which are thought to regulate cancer cell survival and growth. Recent studies 
      demonstrate the intriguing role of mTOR to achieve the feat through metabolic 
      reprogramming in cancer. Importantly, not only mTORC1, a well-known regulator of 
      metabolism both in normal and cancer cell, but mTORC2, an essential partner of 
      mTORC1 downstream of growth factor receptor signaling, controls cooperatively 
      specific metabolism, which nominates them as an essential regulator of cancer 
      metabolism as well as a promising candidate to garner and convey the nutrient 
      information from the surrounding environment. In this article, we depict the 
      recent findings on the role of mTOR complexes in cancer as a master regulator of 
      cancer metabolism and a potential sensor of nutrients, especially focusing on 
      glucose and amino acid sensing in cancer. Novel and detailed molecular mechanisms 
      that amino acids activate mTOR complexes signaling have been identified. We would 
      also like to mention the intricate crosstalk between glucose and amino acid 
      metabolism that ensures the survival of cancer cells, but at the same time it 
      could be exploitable for the novel intervention to target the metabolic 
      vulnerabilities of cancer cells.
FAU - Harachi, Mio
AU  - Harachi M
AD  - Department of Pathology, Division of Pathological Neuroscience, Tokyo Women's 
      Medical University, Tokyo 162-8666, Japan. harachi.mio@twmu.ac.jp.
FAU - Masui, Kenta
AU  - Masui K
AD  - Department of Pathology, Division of Pathological Neuroscience, Tokyo Women's 
      Medical University, Tokyo 162-8666, Japan. masui-kn@twmu.ac.jp.
FAU - Okamura, Yukinori
AU  - Okamura Y
AD  - Department of Pathology, Division of Pathological Neuroscience, Tokyo Women's 
      Medical University, Tokyo 162-8666, Japan. y.okamura.vtol.osprey@gmail.com.
FAU - Tsukui, Ryota
AU  - Tsukui R
AD  - Department of Pathology, Division of Pathological Neuroscience, Tokyo Women's 
      Medical University, Tokyo 162-8666, Japan. tsukuryo0525@gmail.com.
FAU - Mischel, Paul S
AU  - Mischel PS
AD  - Ludwig Institute for Cancer Research, University of California San Diego, La 
      Jolla, CA 92093, USA. pmischel@ucsd.edu.
FAU - Shibata, Noriyuki
AU  - Shibata N
AD  - Department of Pathology, Division of Pathological Neuroscience, Tokyo Women's 
      Medical University, Tokyo 162-8666, Japan. shibatan@twmu.ac.jp.
LA  - eng
GR  - R01 NS073831/NS/NINDS NIH HHS/United States
GR  - 17K15672/Japan Society for the Promotion of Science/
PT  - Journal Article
PT  - Review
DEP - 20181021
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
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  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/*metabolism
MH  - Glucose/*metabolism
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1/genetics/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/genetics/*metabolism
MH  - *Signal Transduction
PMC - PMC6214109
OTO - NOTNLM
OT  - cancer
OT  - mTOR complex
OT  - metabolic reprogramming
OT  - microenvironment
OT  - nutrient sensor
COIS- P.S.M. is a scientific co-founder and consultant for Pretzel Therapeutics, Inc.
EDAT- 2018/10/24 06:00
MHDA- 2019/01/30 06:00
PMCR- 2018/10/01
CRDT- 2018/10/24 06:00
PHST- 2018/09/16 00:00 [received]
PHST- 2018/10/14 00:00 [revised]
PHST- 2018/10/14 00:00 [accepted]
PHST- 2018/10/24 06:00 [entrez]
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2019/01/30 06:00 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - ijms19103267 [pii]
AID - ijms-19-03267 [pii]
AID - 10.3390/ijms19103267 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Oct 21;19(10):3267. doi: 10.3390/ijms19103267.