An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival

A better understanding of the metabolic constraints of a tumor may lead to more effective anticancer treatments. Evidence has emerged in recent years shedding light on a crucial aspartate dependency of many tumor types. As a precursor for nucleotide synthesis, aspartate is indispensable for cell pro...

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Autores principales:	Iiro Taneli Helenius, Hanumantha Rao Madala, Jing-Ruey Joanna Yeh
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oxidative phosphorylation mitochondrial respiration mitochondrial DNA mutation hypoxia aspartate glutaminase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/062bd5e7400a4d539b3f16dfaf731977
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spelling	oai:doaj.org-article:062bd5e7400a4d539b3f16dfaf7319772021-11-25T16:53:33ZAn Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival10.3390/biom111116662218-273Xhttps://doaj.org/article/062bd5e7400a4d539b3f16dfaf7319772021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1666https://doaj.org/toc/2218-273XA better understanding of the metabolic constraints of a tumor may lead to more effective anticancer treatments. Evidence has emerged in recent years shedding light on a crucial aspartate dependency of many tumor types. As a precursor for nucleotide synthesis, aspartate is indispensable for cell proliferation. Moreover, the malate–aspartate shuttle plays a key role in redox balance, and a deficit in aspartate can lead to oxidative stress. It is now recognized that aspartate biosynthesis is largely governed by mitochondrial metabolism, including respiration and glutaminolysis in cancer cells. Therefore, under conditions that suppress mitochondrial metabolism, including mutations, hypoxia, or chemical inhibitors, aspartate can become a limiting factor for tumor growth and cancer cell survival. Notably, aspartate availability has been associated with sensitivity or resistance to various therapeutics that are presently in the clinic or in clinical trials, arguing for a critical need for more effective aspartate-targeting approaches. In this review, we present current knowledge of the metabolic roles of aspartate in cancer cells and describe how cancer cells maintain aspartate levels under different metabolic states. We also highlight several promising aspartate level-modulating agents that are currently under investigation.Iiro Taneli HeleniusHanumantha Rao MadalaJing-Ruey Joanna YehMDPI AGarticleoxidative phosphorylationmitochondrial respirationmitochondrial DNA mutationhypoxiaaspartateglutaminaseMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1666, p 1666 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oxidative phosphorylation mitochondrial respiration mitochondrial DNA mutation hypoxia aspartate glutaminase Microbiology QR1-502
spellingShingle	oxidative phosphorylation mitochondrial respiration mitochondrial DNA mutation hypoxia aspartate glutaminase Microbiology QR1-502 Iiro Taneli Helenius Hanumantha Rao Madala Jing-Ruey Joanna Yeh An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
description	A better understanding of the metabolic constraints of a tumor may lead to more effective anticancer treatments. Evidence has emerged in recent years shedding light on a crucial aspartate dependency of many tumor types. As a precursor for nucleotide synthesis, aspartate is indispensable for cell proliferation. Moreover, the malate–aspartate shuttle plays a key role in redox balance, and a deficit in aspartate can lead to oxidative stress. It is now recognized that aspartate biosynthesis is largely governed by mitochondrial metabolism, including respiration and glutaminolysis in cancer cells. Therefore, under conditions that suppress mitochondrial metabolism, including mutations, hypoxia, or chemical inhibitors, aspartate can become a limiting factor for tumor growth and cancer cell survival. Notably, aspartate availability has been associated with sensitivity or resistance to various therapeutics that are presently in the clinic or in clinical trials, arguing for a critical need for more effective aspartate-targeting approaches. In this review, we present current knowledge of the metabolic roles of aspartate in cancer cells and describe how cancer cells maintain aspartate levels under different metabolic states. We also highlight several promising aspartate level-modulating agents that are currently under investigation.
format	article
author	Iiro Taneli Helenius Hanumantha Rao Madala Jing-Ruey Joanna Yeh
author_facet	Iiro Taneli Helenius Hanumantha Rao Madala Jing-Ruey Joanna Yeh
author_sort	Iiro Taneli Helenius
title	An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
title_short	An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
title_full	An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
title_fullStr	An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
title_full_unstemmed	An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
title_sort	asp to strike out cancer? therapeutic possibilities arising from aspartate’s emerging roles in cell proliferation and survival
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/062bd5e7400a4d539b3f16dfaf731977
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An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival

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