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Title: Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer

Abstract

Aberrant glutamatergic signaling has been implicated in altered metabolic activity and the demand to synthesize biomass in several types of cancer including melanoma. In the last decade, there has been a significant contribution to our understanding of metabolic pathways. An increasing number of studies are now emphasizing the importance of glutamate functioning as a signaling molecule and a building block for cancer progression. To that end, our group has previously illustrated the role of glutamatergic signaling mediated by metabotropic glutamate receptor 1 (GRM1) in neoplastic transformation of melanocytes in vitro and spontaneous development of metastatic melanoma in vivo. Glutamate, the natural ligand of GRM1, is one of the most abundant amino acids in humans and the predominant excitatory neurotransmitter in the central nervous system. Elevated levels of glutaminolytic mitochondrial tricarboxylic acid (TCA) cycle intermediates, especially glutamate, have been reported in numerous cancer cells. Herein, we highlight and critically review metabolic bottlenecks that are prevalent during tumor evolution along with therapeutic implications of limiting glutamate bioavailability in tumors.

Authors:
ORCiD logo;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1660318
Grant/Contract Number:  
R44CA156781
Resource Type:
Published Article
Journal Name:
Cancers (Basel)
Additional Journal Information:
Journal Name: Cancers (Basel) Journal Volume: 12 Journal Issue: 9; Journal ID: ISSN 2072-6694
Publisher:
MDPI AG
Country of Publication:
Switzerland
Language:
English

Citation Formats

Shah, Raj, and Chen, Suzie. Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer. Switzerland: N. p., 2020. Web. https://doi.org/10.3390/cancers12092624.
Shah, Raj, & Chen, Suzie. Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer. Switzerland. https://doi.org/10.3390/cancers12092624
Shah, Raj, and Chen, Suzie. Mon . "Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer". Switzerland. https://doi.org/10.3390/cancers12092624.
@article{osti_1660318,
title = {Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer},
author = {Shah, Raj and Chen, Suzie},
abstractNote = {Aberrant glutamatergic signaling has been implicated in altered metabolic activity and the demand to synthesize biomass in several types of cancer including melanoma. In the last decade, there has been a significant contribution to our understanding of metabolic pathways. An increasing number of studies are now emphasizing the importance of glutamate functioning as a signaling molecule and a building block for cancer progression. To that end, our group has previously illustrated the role of glutamatergic signaling mediated by metabotropic glutamate receptor 1 (GRM1) in neoplastic transformation of melanocytes in vitro and spontaneous development of metastatic melanoma in vivo. Glutamate, the natural ligand of GRM1, is one of the most abundant amino acids in humans and the predominant excitatory neurotransmitter in the central nervous system. Elevated levels of glutaminolytic mitochondrial tricarboxylic acid (TCA) cycle intermediates, especially glutamate, have been reported in numerous cancer cells. Herein, we highlight and critically review metabolic bottlenecks that are prevalent during tumor evolution along with therapeutic implications of limiting glutamate bioavailability in tumors.},
doi = {10.3390/cancers12092624},
journal = {Cancers (Basel)},
number = 9,
volume = 12,
place = {Switzerland},
year = {2020},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.3390/cancers12092624

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