PMID- 28202352
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20190221
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 393
DP  - 2017 May 1
TI  - Amino acid transporter SLC38A3 promotes metastasis of non-small cell lung cancer 
      cells by activating PDK1.
PG  - 8-15
LID - S0304-3835(17)30078-2 [pii]
LID - 10.1016/j.canlet.2017.01.036 [doi]
AB  - BACKGROUND: Tumor metastasis is a finely-tuned pathological process coupled to 
      metabolic reprogramming that includes both glutamine and glucose. The solute 
      carrier SLC38A3, a member of amino acid/polyamine/organocation (APC) superfamily, 
      is an l-glutamine transporter. It is not clear whether SLC38A3 involves the 
      metastasis of NSCLC (non small cell lung cancer). METHODS: The scratch test and 
      transwell assay were used to determine the ability of NSCLC to migrate. Cellular 
      amino acids content was determined by mass spectrometry. The cellular response to 
      glutamine/histidine deficiency was evaluated in A549 cells. The expression of 
      SLC38A3 was assayed in clinical NSCLC and paratumor tissues by 
      histoimmunochemistry staining. A nude mouse model of NSCLC metastasis was 
      developed by tail vein injection of tumor cells. RESULTS: SLC38A3 was upregulated 
      in metastatic NSCLC cells and its expression was correlated with prognosis of 
      NSCLC patients. SLC38A3 overexpression promoted epithelial - mesenchymal 
      transition (EMT) and migration of HCC827 and A549 human lung adenocarcinoma 
      cells, and accelerated tumor metastasis in mice. We found that SLC38A3 decreased 
      the cellular concentrations of glutamine and histidine, and the deficiency of 
      glutamine or histidine activated PDK1/AKT signaling that in turn, triggered NSCLC 
      metastasis. CONCLUSIONS: SLC38A3 activated PDK1/AKT signaling and promoted 
      metastasis of NSCLC through regulating glutamine and histidine transport, 
      suggesting SLC38A3 as a potential therapeutic target for treatment of NSCLC.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Wang, Yanhui
AU  - Wang Y
AD  - Department of Biochemistry & Molecular Cell Biology, Key Laboratory of Cell 
      Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao 
      Tong University School of Medicine, China; Dalian Medical University Institute of 
      Cancer Stem Cell, China. Electronic address: wangyanh123@sina.cn.
FAU - Fu, Li
AU  - Fu L
AD  - Department of Biochemistry & Molecular Cell Biology, Key Laboratory of Cell 
      Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao 
      Tong University School of Medicine, China; Dalian Medical University Institute of 
      Cancer Stem Cell, China. Electronic address: auojn@163.com.
FAU - Cui, Minqing
AU  - Cui M
AD  - Department of Biochemistry & Molecular Cell Biology, Key Laboratory of Cell 
      Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao 
      Tong University School of Medicine, China. Electronic address: 
      13817211597@163.com.
FAU - Wang, Yongbin
AU  - Wang Y
AD  - Department of Biochemistry & Molecular Cell Biology, Key Laboratory of Cell 
      Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao 
      Tong University School of Medicine, China. Electronic address: wybzyp@126.com.
FAU - Xu, Yan
AU  - Xu Y
AD  - Department of Biochemistry & Molecular Cell Biology, Key Laboratory of Cell 
      Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao 
      Tong University School of Medicine, China. Electronic address: 
      yan_xu@sjtu.edu.cn.
FAU - Li, Molin
AU  - Li M
AD  - Dalian Medical University Institute of Cancer Stem Cell, China. Electronic 
      address: molin_li@hotmail.com.
FAU - Mi, Jun
AU  - Mi J
AD  - Department of Biochemistry & Molecular Cell Biology, Key Laboratory of Cell 
      Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao 
      Tong University School of Medicine, China. Electronic address: jmei@sjtu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170213
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (SLC38A3 protein, human)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 4QD397987E (Histidine)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases/genetics/*metabolism
MH  - A549 Cells
MH  - Adenocarcinoma/*enzymology/genetics/*pathology
MH  - Adenocarcinoma of Lung
MH  - Animals
MH  - Carcinoma, Non-Small-Cell Lung/*enzymology/genetics/*secondary
MH  - *Cell Movement
MH  - Enzyme Activation
MH  - Epithelial-Mesenchymal Transition
MH  - Glutamic Acid/deficiency
MH  - Histidine/deficiency
MH  - Humans
MH  - Lung Neoplasms/*enzymology/genetics/*pathology
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - Sodium-Calcium Exchanger/genetics/*metabolism
MH  - Transfection
OTO - NOTNLM
OT  - Glutamine
OT  - Metastasis
OT  - NSCLC
OT  - PDK1
OT  - SLC38A3
EDAT- 2017/02/17 06:00
MHDA- 2017/08/15 06:00
CRDT- 2017/02/17 06:00
PHST- 2016/11/01 00:00 [received]
PHST- 2017/01/25 00:00 [revised]
PHST- 2017/01/25 00:00 [accepted]
PHST- 2017/02/17 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2017/02/17 06:00 [entrez]
AID - S0304-3835(17)30078-2 [pii]
AID - 10.1016/j.canlet.2017.01.036 [doi]
PST - ppublish
SO  - Cancer Lett. 2017 May 1;393:8-15. doi: 10.1016/j.canlet.2017.01.036. Epub 2017 
      Feb 13.