P0143 ASC amino acid transporter 2 (ASCT2) as a novel prognostic marker in non-small-cell lung cancer

Shimizu, Keiichiro; Kaira, Kyoichi; Tomizawa, Yoshio; Sunaga, Noriaki; Kawashima, Osamu; Oriuchi, Noboru; Kana, Y.; Yamada, M; Oyama, Tetsunari; Takeyoshi, Izumi

doi:10.1016/j.ejca.2014.03.187

Cited by 2 publications

(2 citation statements)

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“…However, in normal rat astrocytes in situ , glutamine transport is mediated by a Na + -dependent system N, SN1 [ 20 ]. During transformation, ASCT2 and LAT1 are the two main transporters for glutamine uptake [ 22 , 23 , 24 ]. It has been hypothesized that LAT1 provides the essential amino acids to enhance cancer cell growth via mTOR-stimulated translation, and that ASCT2 maintains the cytoplasmic amino acid pool to drive LAT1 function [ 18 ].…”

Section: Glutamine Metabolismmentioning

confidence: 99%

Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

Chen

Cui

2015

IJMS

133

101

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Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to cells by specific transporters and converted to glutamate by glutaminase. There are currently several drugs that target glutaminase under development or clinical trials. Also, glutamine metabolism restriction has been proved to be effective in inhibiting tumor growth both in vivo and vitro through inducing apoptosis, growth arrest and/or autophagy. Here, we review recent researches about glutamine metabolism in cancer, and cell death induced by targeting glutamine, and their potential roles in cancer therapy.

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Section: Glutamine Metabolismmentioning

confidence: 99%

Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

Chen

Cui

2015

IJMS

133

101

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“…Activated mTOR then promotes protein translation and cell growth via activation of its downstream genes such as S6k1 and 4EBP1 [24]. Alanine, serine, cysteine-preferring transporter 2 (ASCT2), also known as (SLC1A5), and bidirectional L-type amino acid transporter 1 (LAT1) are the two primary transporters for glutamine uptake [25,26]. LAT1 enables transport of the EAAs to improve cancer cell growth via mTOR-induced translations, and ASCT2 sustains the cytoplasmic amino acid pool to drive LAT1 function [27].…”

Section: Introductionmentioning

confidence: 99%

Delta-Tocotrienol Modulates Glutamine Dependence by Inhibiting ASCT2 and LAT1 Transporters in Non-Small Cell Lung Cancer (NSCLC) Cells: A Metabolomic Approach

2019

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The growth and development of non-small cell lung cancer (NSCLC) primarily depends on glutamine. Both glutamine and essential amino acids (EAAs) have been reported to upregulate mTOR in NSCLC, which is a bioenergetics sensor involved in the regulation of cell growth, cell survival, and protein synthesis. Seen as novel concepts in cancer development, ASCT2 and LAT transporters allow glutamine and EAAs to enter proliferating tumors as well as send a regulatory signal to mTOR. Blocking or downregulating these glutamine transporters in order to inhibit glutamine uptake would be an excellent therapeutic target for treatment of NSCLC. This study aimed to validate the metabolic dysregulation of glutamine and its derivatives in NSCLC using cellular 1H-NMR metabolomic approach while exploring the mechanism of delta-tocotrienol (δT) on glutamine transporters, and mTOR pathway. Cellular metabolomics analysis showed significant inhibition in the uptake of glutamine, its derivatives glutamate and glutathione, and some EAAs in both cell lines with δT treatment. Inhibition of glutamine transporters (ASCT2 and LAT1) and mTOR pathway proteins (P-mTOR and p-4EBP1) was evident in Western blot analysis in a dose-dependent manner. Our findings suggest that δT inhibits glutamine transporters, thus inhibiting glutamine uptake into proliferating cells, which results in the inhibition of cell proliferation and induction of apoptosis via downregulation of the mTOR pathway.

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P0143 ASC amino acid transporter 2 (ASCT2) as a novel prognostic marker in non-small-cell lung cancer

Cited by 2 publications

References 0 publications

Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

Delta-Tocotrienol Modulates Glutamine Dependence by Inhibiting ASCT2 and LAT1 Transporters in Non-Small Cell Lung Cancer (NSCLC) Cells: A Metabolomic Approach

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