Cysteine metabolic circuitries: druggable targets in cancer
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TLDR
This review will provide a systematic portrayal of the role of cysteine in cancer biology as a source of carbon and sulphur atoms, the pivotal role in different metabolic pathways and the importance of H2S as an energetic substrate and signalling molecule.Abstract:
To enable survival in adverse conditions, cancer cells undergo global metabolic adaptations. The amino acid cysteine actively contributes to cancer metabolic remodelling on three different levels: first, in its free form, in redox control, as a component of the antioxidant glutathione or its involvement in protein s-cysteinylation, a reversible post-translational modification; second, as a substrate for the production of hydrogen sulphide (H2S), which feeds the mitochondrial electron transfer chain and mediates per-sulphidation of ATPase and glycolytic enzymes, thereby stimulating cellular bioenergetics; and, finally, as a carbon source for epigenetic regulation, biomass production and energy production. This review will provide a systematic portrayal of the role of cysteine in cancer biology as a source of carbon and sulphur atoms, the pivotal role of cysteine in different metabolic pathways and the importance of H2S as an energetic substrate and signalling molecule. The different pools of cysteine in the cell and within the body, and their putative use as prognostic cancer markers will be also addressed. Finally, we will discuss the pharmacological means and potential of targeting cysteine metabolism for the treatment of cancer.read more
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mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient
Gregory A. Wyant,Monther Abu-Remaileh,Rachel L. Wolfson,Walter W. Chen,Elizaveta Freinkman,Laura V. Danai,Matthew G. Vander Heiden,Matthew G. Vander Heiden,David M. Sabatini +8 more
TL;DR: In this article, the authors validate that SLC38A9 is an arginine sensor for the mTORC1 pathway, and uncover an unexpectedly central role for SLC 38A9 in amino acid homeostasis.
Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development
Qian Wang,Qian Wang,Rae-Anne Hardie,Rae-Anne Hardie,Andrew J. Hoy,Michelle van Geldermalsen,Michelle van Geldermalsen,Dadi Gao,Dadi Gao,Ladan Fazli,Martin C. Sadowski,Seher Balaban,Mark Schreuder,Rajini Nagarajah,Rajini Nagarajah,Justin J.-L. Wong,Justin J.-L. Wong,Cynthia Metierre,Cynthia Metierre,Natalia Pinello,Natalia Pinello,Nicholas J. Otte,Nicholas J. Otte,Melanie Lehman,Martin E. Gleave,Colleen C. Nelson,Charles G. Bailey,Charles G. Bailey,William Ritchie,William Ritchie,John E.J. Rasko,John E.J. Rasko,John E.J. Rasko,Jeff Holst,Jeff Holst +34 more
TL;DR: This article showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth.
Journal ArticleDOI
Physiological roles of hydrogen sulfide in mammalian cells, tissues and organs.
TL;DR: A wide array of significant roles of H2S in the physiological regulation of all organ functions emerges from this review.
Journal ArticleDOI
Metabolic Reprogramming in Anticancer Drug Resistance: A Focus on Amino Acids.
TL;DR: Recent evidence highlighting the key role of amino acid (AA) metabolic reprogramming in cancer cells and the supportive microenvironment in driving resistance to anticancer therapies is provided.
References
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H2S Signals Through Protein S-Sulfhydration
Asif K. Mustafa,Moataz M. Gadalla,Nilkantha Sen,Seyun Kim,Weitong Mu,Sadia K. Gazi,Roxanne K. Barrow,Guangdong Yang,Rui Wang,Solomon H. Snyder +9 more
TL;DR: Ex vivo endogenous H2S physiologically modifies cysteine residues in many proteins, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and actin, converting Cysteine -SH groups to -SSH groups in a process the authors call S-sulfhydration.