Nonessential amino acid metabolism in breast cancer.

Interest in studying cancer metabolism has risen in recent years, as it has become evident that the relationship between cancer and metabolic pathways could reveal novel biomarkers and therapeutic targets. Metabolic starvation therapy is particularly promising due to its low toxicity. Nonessential amino acids are promising metabolites for such therapy because they become essential in many tumor cells, including breast cancer cells. This review will focus on four nonessential amino acid metabolism pathways: glutamine-glutamate, serine-glycine, cysteine, and arginine-proline metabolism. Recent studies of these amino acids have revealed metabolic enzymes that have the potential to be effective as cancer therapy targets or biomarkers for response to metabolic starvation therapy. The review will also discuss features of nonessential amino acid metabolism that merit further investigation to determine their relevancy to breast cancer treatment.

[1]  W. Jung,et al.  Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. , 2013, Endocrine-related cancer.

[2]  Gregory Stephanopoulos,et al.  Amplification of phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis , 2012, BMC Proceedings.

[3]  M. Medina,et al.  Glutamine and cancer. , 2001, The Journal of nutrition.

[4]  L. Cantley,et al.  Genetic selection for enhanced serine metabolism in cancer development , 2011, Cell cycle.

[5]  Stephen L. Abrams,et al.  Targeting breast cancer initiating cells: advances in breast cancer research and therapy. , 2014, Advances in biological regulation.

[6]  G. Michailidis,et al.  EMT-induced metabolite signature identifies poor clinical outcome , 2015, Oncotarget.

[7]  Yixiang Duan,et al.  Investigation of salivary free amino acid profile for early diagnosis of breast cancer with ultra performance liquid chromatography-mass spectrometry. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[8]  Oliver Fiehn,et al.  Comparative metabolomics of estrogen receptor positive and estrogen receptor negative breast cancer: alterations in glutamine and beta-alanine metabolism. , 2013, Journal of proteomics.

[9]  Wei Liu,et al.  Proline metabolism and cancer: emerging links to glutamine and collagen , 2014, Current opinion in clinical nutrition and metabolic care.

[10]  Wen-Ren Wu,et al.  ASS1 as a Novel Tumor Suppressor Gene in Myxofibrosarcomas: Aberrant Loss via Epigenetic DNA Methylation Confers Aggressive Phenotypes, Negative Prognostic Impact, and Therapeutic Relevance , 2013, Clinical Cancer Research.

[11]  J. Madelmont,et al.  Methionine dependency and cancer treatment. , 2003, Cancer treatment reviews.

[12]  R. Clarke,et al.  MYC regulates the unfolded protein response and glucose and glutamine uptake in endocrine resistant breast cancer , 2014, Molecular Cancer.

[13]  R. Steele,et al.  Arginine metabolism in benign and malignant disease of breast and colon: evidence for possible inhibition of tumor-infiltrating macrophages. , 1991, Nutrition.

[14]  M. Morello,et al.  Bioinformatics analysis of the serine and glycine pathway in cancer cells , 2014, Oncotarget.

[15]  Y. Yen,et al.  Arginine Starvation Impairs Mitochondrial Respiratory Function in ASS1-Deficient Breast Cancer Cells , 2014, Science Signaling.

[16]  O. Fiehn,et al.  Glutamate enrichment as new diagnostic opportunity in breast cancer , 2015, International journal of cancer.

[17]  Carlotta Granchi,et al.  An update on therapeutic opportunities offered by cancer glycolytic metabolism. , 2014, Bioorganic & medicinal chemistry letters.

[18]  R. Hoffman.  Development of recombinant methioninase to target the general cancer-specific metabolic defect of methionine dependence: a 40-year odyssey , 2015, Expert opinion on biological therapy.

[19]  I. Amelio,et al.  Serine and glycine metabolism in cancer☆ , 2014, Trends in biochemical sciences.

[20]  M. Lai,et al.  Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer , 2014, Oncology reports.

[21]  B. Faubert,et al.  PGC-1α supports glutamine metabolism in breast cancer , 2013, Cancer & Metabolism.

[22]  K. Vousden,et al.  Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. , 2014, Cell reports.

[23]  J. Bomalaski,et al.  Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. , 2002, Cancer research.

[24]  W. Jung,et al.  Expression levels of serine/glycine metabolism-related proteins in triple negative breast cancer tissues , 2014, Tumor Biology.

[25]  J. Locasale.  Serine, glycine and one-carbon units: cancer metabolism in full circle , 2013, Nature Reviews Cancer.

[26]  G. Chaudhuri,et al.  Activation of caspase-3 activity and apoptosis in MDA-MB-468 cells by N(omega)-hydroxy-L-arginine, an inhibitor of arginase, is not solely dependent on reduction in intracellular polyamines. , 2001, Carcinogenesis.

[27]  F. Qiu,et al.  Targeting arginine metabolism pathway to treat arginine-dependent cancers. , 2015, Cancer letters.

[28]  G. Palumbo,et al.  Cells derived from normal or cancer breast tissue exhibit different growth properties when deprived of arginine , 2012, Medical Oncology.

[29]  Stephanie M. Tortorella,et al.  The Warburg effect: molecular aspects and therapeutic possibilities , 2014, Molecular Biology Reports.

[30]  J. Erickson,et al.  Glutaminase: A Hot Spot For Regulation Of Cancer Cell Metabolism? , 2010, Oncotarget.

[31]  C. Dejong,et al.  Plasma arginine concentrations are reduced in cancer patients: evidence for arginine deficiency? , 2005, The American journal of clinical nutrition.

[32]  Young‐Tae Chang,et al.  Effect of oncogene activating mutations and kinase inhibitors on amino acid metabolism of human isogenic breast cancer cells. , 2015, Molecular bioSystems.

[33]  W. Ritchie,et al.  ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer , 2015, Oncogene.

[34]  J. Yarnold,et al.  Treatment of breast cancer , 1994, The Lancet.

[35]  S. Curley,et al.  Incidence and distribution of argininosuccinate synthetase deficiency in human cancers , 2004, Cancer.

[36]  Keith W Kelley,et al.  NIH public access policy , 2008, Brain, Behavior, and Immunity.

[37]  Meng Yang,et al.  Human tumor growth in nude mice is associated with decreased plasma cysteine and homocysteine. , 2008, Anticancer research.

[38]  C. Speyer,et al.  Metabotropic glutamate receptor-1: a potential therapeutic target for the treatment of breast cancer , 2012, Breast Cancer Research and Treatment.

[39]  T. Bathen,et al.  Metabolic characterization of triple negative breast cancer , 2014, BMC Cancer.

[40]  이연수.  Functional genomics reveal that the serine synthesis pathway is essential in breast cancer , 2011 .

[41]  Stephen L. Abrams,et al.  Roles of signaling pathways in drug resistance, cancer initiating cells and cancer progression and metastasis. , 2015, Advances in biological regulation.

[42]  Ludmila V. Danilova,et al.  Frequent Inactivation of Cysteine Dioxygenase Type 1 Contributes to Survival of Breast Cancer Cells and Resistance to Anthracyclines , 2013, Clinical Cancer Research.

[43]  S. Morris,et al.  Recent advances in arginine metabolism: roles and regulation of the arginases. , 2009, British journal of pharmacology.

[44]  V. Mootha,et al.  Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation , 2012, Science.

[45]  K. Kang,et al.  Elevation of cysteine consumption in tamoxifen-resistant MCF-7 cells. , 2013, Biochemical pharmacology.

[46]  Frank Y. S. Chuang,et al.  Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy , 2014, Proceedings of the National Academy of Sciences.

[47]  O. Warburg.  [Origin of cancer cells]. , 1956, Oncologia.

[48]  S. Cederbaum,et al.  Arginase activity in human breast cancer cell lines: N(omega)-hydroxy-L-arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells. , 2000, Cancer research.

[49]  S. Kaore,et al.  Citrulline: pharmacological perspectives and its role as an emerging biomarker in future , 2013, Fundamental & clinical pharmacology.

[50]  K. Kang,et al.  Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells. , 2011, Toxicology and applied pharmacology.

[51]  B. Kholodenko,et al.  The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance cancer cell motility , 2014, Science Signaling.

[52]  Tomer Shlomi,et al.  Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia , 2013, Molecular systems biology.

[53]  M. Amiji,et al.  Tumor aerobic glycolysis: new insights into therapeutic strategies with targeted delivery , 2014, Expert opinion on biological therapy.

[54]  R. Deberardinis.  Serine metabolism: some tumors take the road less traveled. , 2011, Cell metabolism.

[55]  Seong-Yun Jeong,et al.  Arginine deiminase enhances MCF-7 cell radiosensitivity by inducing changes in the expression of cell cycle-related proteins. , 2008, Molecules and cells.

[56]  W W Souba,et al.  Glutamine and Cancer , 1993, Annals of surgery.

[57]  W. Jung,et al.  Differential Expression of Enzymes Associated with Serine/Glycine Metabolism in Different Breast Cancer Subtypes , 2014, PloS one.

[58]  Soo‐Youl Kim.  Cancer Metabolism: Strategic Diversion from Targeting Cancer Drivers to Targeting Cancer Suppliers , 2015, Biomolecules & therapeutics.

[59]  Jeffrey W. Smith,et al.  Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies. , 2015, Cancer cell.

[60]  B. Delage,et al.  Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer , 2010, International journal of cancer.

[61]  Zhen-Yu You,et al.  Analyzing the differentially expressed genes and pathway cross‐talk in aggressive breast cancer , 2015, The journal of obstetrics and gynaecology research.

[62]  J. Lamb,et al.  Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells , 2000, British Journal of Cancer.

[63]  A. Jemal,et al.  Cancer statistics, 2015 , 2015, CA: a cancer journal for clinicians.