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The Diverse Functions of Non-Essential Amino Acids in Cancer
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The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival

Department of Cancer Physiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
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Cancers 2019, 11(5), 678; https://doi.org/10.3390/cancers11050678
Received: 24 April 2019 / Revised: 13 May 2019 / Accepted: 14 May 2019 / Published: 16 May 2019
(This article belongs to the Special Issue Metabolic Reprogramming and Vulnerabilities in Cancer)
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Abstract

The non-essential amino acid cysteine is used within cells for multiple processes that rely on the chemistry of its thiol group. Under physiological conditions, many non-transformed tissues rely on glutathione, circulating cysteine, and the de novo cysteine synthesis (transsulfuration) pathway as sources of intracellular cysteine to support cellular processes. In contrast, many cancers require exogeneous cystine for proliferation and viability. Herein, we review how the cystine transporter, xCT, and exogenous cystine fuel cancer cell proliferation and the mechanisms that regulate xCT expression and activity. Further, we discuss the potential contribution of additional sources of cysteine to the cysteine pool and what is known about the essentiality of these processes in cancer cells. Finally, we discuss whether cyst(e)ine dependency and associated metabolic alterations represent therapeutically targetable metabolic vulnerabilities. View Full-Text
Keywords: cystine; cysteine; xCT; transsulfuration; glutathione; macropinocytosis; cystathionine; CBS; CSE; GGT cystine; cysteine; xCT; transsulfuration; glutathione; macropinocytosis; cystathionine; CBS; CSE; GGT
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Combs, J.A.; DeNicola, G.M. The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival. Cancers 2019, 11, 678.

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