Ovarian cancer therapeutic potential of glutamine depletion based on GS expression.

Abstract:

:Amino acids (AAs) are biologically important nutrient compounds necessary for the survival of any cell. Of the 20 AAs, cancer cells depend on the uptake of several extracellular AAs for survival. However, which extracellular AA is indispensable for the survival of cancer cells and the molecular mechanism involved have not been fully defined. In this study, we found that the reduction of cell survival caused by glutamine (Gln) depletion is inversely correlated with the expression level of glutamine synthetase (GS) in ovarian cancer (OVC) cells. GS expression was downregulated in 45 of 316 OVC cases (14.2%). The depletion of extracellular Gln by treatment with l-asparaginase, in addition to inhibiting Gln uptake via the knockdown of a Gln transporter, led to the inhibition of cell growth in OVC cells with low expression of GS (GSlow-OVC cells). Furthermore, the re-expression of GS in GSlow-OVC cells induced the inhibition of tumor growth in vitro and in vivo. Thus, these findings provide novel insight into the development of an OVC therapy based on the requirement of Gln.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Furusawa A,Miyamoto M,Takano M,Tsuda H,Song YS,Aoki D,Miyasaka N,Inazawa J,Inoue J

doi

10.1093/carcin/bgy033

subject

Has Abstract

pub_date

2018-05-28 00:00:00

pages

758-766

issue

6

eissn

0143-3334

issn

1460-2180

pii

4956801

journal_volume

39

pub_type

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