Targeting extracellular nutrient dependencies of cancer cells

García‐Bermúdez, Javier; Williams, Robert T.; Guarecuco, Rohiverth; Birsoy, Kıvanç

doi:10.1016/j.molmet.2019.11.011

Cited by 63 publications

(47 citation statements)

References 206 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, L-asparaginase (ASNase) treatment in ALL patients catalyzes the conversion of plasma L-asparagine to aspartic acid and ammonia, leading to the death of cancer cells due to the inhibited global protein synthesis. Similarly, deterioration of asparagine uptake might also cause the death of ALL but not normal cells [ 149 , 150 , 151 , 152 ].…”

Section: Amino Acid Transporters As Targets For Tumor Treatmentmentioning

confidence: 99%

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Kahya

Köseer

Dubrovska

2021

Cancers

View full text Add to dashboard Cite

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

show abstract

Section: Amino Acid Transporters As Targets For Tumor Treatmentmentioning

confidence: 99%

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Kahya

Köseer

Dubrovska

2021

Cancers

View full text Add to dashboard Cite

show abstract

“…This reversible reaction occurs via two half-reactions in a “ping-pong” mechanism, the first comprising the reaction of the PLP moiety with l -aspartate, yielding pyridoxamine 5′-phosphate (PMP) and OAA; and the second consisting of the reverse of this half-reaction with α-ketoglutarate, restoring PLP and generating l -glutamate [ 19 ]. Once aspartate levels decrease, CAT can: (i) Reverse the flux to generate rather than consume aspartate (upon mitochondrial electron transfer chain dysfunction [ 19 , 64 ]), which is required for purine and pyrimidine synthesis; (ii) sustain the urea cycle by acting as a nitrogen donor [ 65 ]; and (iii) underlie the production of arginine as well as asparagine, by the catalysis of asparagine synthetase [ 66 ].…”

Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

“…Aspartate is essential for cancer cells to survive and proliferate, since it is the precursor in several pathways, including the synthesis of asparagine, as mentioned. Certain subsets of acute lymphoblastic leukemia cells are unable to synthesize asparagine and thrive on extracellular asparagine production to sustain proliferation and survival, thus being dependent on the functioning of CAT [ 66 ].…”

Section: Cat Role In Physiology and In Cancermentioning

confidence: 99%

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Hipólito

Nunes

Vicente³

et al. 2020

Molecules

View full text Add to dashboard Cite

Metabolic remodeling is a critical skill of malignant cells, allowing their survival and spread. The metabolic dynamics and adaptation capacity of cancer cells allow them to escape from damaging stimuli, including breakage or cross-links in DNA strands and increased reactive oxygen species (ROS) levels, promoting resistance to currently available therapies, such as alkylating or oxidative agents. Therefore, it is essential to understand how metabolic pathways and the corresponding enzymatic systems can impact on tumor behavior. Cysteine aminotransferase (CAT) per se, as well as a component of the CAT: 3-mercaptopyruvate sulfurtransferase (MST) axis, is pivotal for this metabolic rewiring, constituting a central mechanism in amino acid metabolism and fulfilling the metabolic needs of cancer cells, thereby supplying other different pathways. In this review, we explore the current state-of-art on CAT function and its role on cancer cell metabolic rewiring as MST partner, and its relevance in cancer cells’ fitness.

show abstract

“…In recent years, it is becoming evident that changes in cell metabolism contribute to cancer development and progression 16‐20 . Converging evidence indicates that the well‐known tumour suppressor p53 controls multiple metabolic pathways and plays a major role in metabolism of cancer cells 20 .…”

Section: Introductionmentioning

confidence: 99%

Combined analysis of RNA‐sequence and microarray data reveals effective metabolism‐based prognostic signature for neuroblastoma

Meng

Feng

Fang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

The relationship between metabolism reprogramming and neuroblastoma (NB) is largely unknown. In this study, one RNA‐sequence data set (n = 153) was used as discovery cohort and two microarray data sets (n = 498 and n = 223) were used as validation cohorts. Differentially expressed metabolic genes were identified by comparing stage 4s and stage 4 NBs. Twelve metabolic genes were selected by LASSO regression analysis and integrated into the prognostic signature. The metabolic gene signature successfully stratifies NB patients into two risk groups and performs well in predicting survival of NB patients. The prognostic value of the metabolic gene signature is also independent with other clinical risk factors. Nine metabolism‐related long non‐coding RNAs (lncRNAs) were also identified and integrated into the metabolism‐related lncRNA signature. The lncRNA signature also performs well in predicting survival of NB patients. These results suggest that the metabolic signatures have the potential to be used for risk stratification of NB. Gene set enrichment analysis (GSEA) reveals that multiple metabolic processes (including oxidative phosphorylation and tricarboxylic acid cycle, both of which are emerging targets for cancer therapy) are enriched in the high‐risk NB group, and no metabolic process is enriched in the low‐risk NB group. This result indicates that metabolism reprogramming is associated with the progression of NB and targeting certain metabolic pathways might be a promising therapy for NB.

show abstract

Targeting extracellular nutrient dependencies of cancer cells

Cited by 63 publications

References 206 publications

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Combined analysis of RNA‐sequence and microarray data reveals effective metabolism‐based prognostic signature for neuroblastoma

Contact Info

Product

Resources

About