Cancer & Metabolism最新文献

{"title":"Caffeic Acid targets metabolism of cervical squamous cell carcinoma","authors":"M. Tyszka-Czochara","doi":"10.1016/B978-0-12-819547-5.00025-0","DOIUrl":"https://doi.org/10.1016/B978-0-12-819547-5.00025-0","url":null,"abstract":"","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"65 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73739338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant vitamins and genetic polymorphisms in breast cancer","authors":"D. Kang, Sang Ah Lee","doi":"10.1016/B978-0-12-405205-5.00016-7","DOIUrl":"https://doi.org/10.1016/B978-0-12-405205-5.00016-7","url":null,"abstract":"","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"216 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75029425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficiency of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis.","authors":"H Furkan Alkan, Paul W Vesely, Hubert Hackl, Johannes Foßelteder, Daniel R Schmidt, Matthew G Vander Heiden, Martin Pichler, Gerald Hoefler, Juliane G Bogner-Strauss","doi":"10.1186/s40170-020-00232-7","DOIUrl":"10.1186/s40170-020-00232-7","url":null,"abstract":"<p><strong>Background: </strong>Aspartate biosynthesis and its delivery to the cytosol can be crucial for tumor growth in vivo. However, the impact of intracellular aspartate levels on metastasis has not been studied. We previously described that loss-of-aspartate glutamate carrier 1 (SLC25A12 or AGC1), an important component of the malate-aspartate shuttle, impairs cytosolic aspartate levels, NAD⁺/NADH ratio, mitochondrial respiration, and tumor growth. Here, we report the impact of AGC1-knockdown on metastasis.</p><p><strong>Results: </strong>Low AGC1 expression correlates with worse patient prognosis in many cancers. AGC1-knockdown in mouse lung carcinoma and melanoma cell lines leads to increased pulmonary metastasis following subcutaneous or intravenous injections, respectively. On the other hand, conventional in vitro metastasis assays show no indication of increased metastasis capacity of AGC1-knockdown cells.</p><p><strong>Conclusion: </strong>This study highlights that certain branches of metabolism impact tumor growth and tumor metastasis differently. In addition, it also argues that commonly known metastasis indicators, including EMT genes, cell migration, or colony formation, do not always reflect metastatic capacity in vivo.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"8 1","pages":"26"},"PeriodicalIF":6.0,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic plasticity of IDH1<i>-mutant</i> glioma cell lines is responsible for low sensitivity to glutaminase inhibition.","authors":"Victor Ruiz-Rodado,&nbsp;Adrian Lita,&nbsp;Tyrone Dowdy,&nbsp;Orieta Celiku,&nbsp;Alejandra Cavazos Saldana,&nbsp;Herui Wang,&nbsp;Chun Zhang Yang,&nbsp;Raj Chari,&nbsp;Aiguo Li,&nbsp;Wei Zhang,&nbsp;Hua Song,&nbsp;Meili Zhang,&nbsp;Susie Ahn,&nbsp;Dionne Davis,&nbsp;Xiang Chen,&nbsp;Zhengping Zhuang,&nbsp;Christel Herold-Mende,&nbsp;Kylie J Walters,&nbsp;Mark R Gilbert,&nbsp;Mioara Larion","doi":"10.1186/s40170-020-00229-2","DOIUrl":"https://doi.org/10.1186/s40170-020-00229-2","url":null,"abstract":"<p><strong>Background: </strong>Targeting glutamine metabolism in cancer has become an increasingly vibrant area of research. Mutant IDH1 (IDH1 ^<i>mut</i> ) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate (2HG).</p><p><strong>Methods: </strong>We have employed a combination of ¹³C tracers including glutamine and glucose for investigating the metabolism of patient-derived IDH1 ^<i>mut</i> glioma cell lines through NMR and LC/MS. Additionally, genetic loss-of-function (in vitro and in vivo) approaches were performed to unravel the adaptability of these cell lines to the inhibition of glutaminase activity.</p><p><strong>Results: </strong>We report the adaptability of IDH1 ^<i>mut</i> cells' metabolism to the inhibition of glutamine/glutamate pathway. The glutaminase inhibitor CB839 generated a decrease in the production of the downstream metabolites of glutamate, including those involved in the TCA cycle and 2HG. However, this effect on metabolism was not extended to viability; rather, our patient-derived IDH1 ^<i>mut</i> cell lines display a metabolic plasticity that allows them to overcome glutaminase inhibition.</p><p><strong>Conclusions: </strong>Major metabolic adaptations involved pathways that can generate glutamate by using alternative substrates from glutamine, such as alanine or aspartate. Indeed, asparagine synthetase was upregulated both in vivo and in vitro revealing a new potential therapeutic target for a combinatory approach with CB839 against IDH1 ^<i>mut</i> gliomas.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"8 ","pages":"23"},"PeriodicalIF":5.9,"publicationDate":"2020-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40170-020-00229-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38527972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating pyrimidine ribonucleotide levels for the treatment of cancer.","authors":"Tanzina Mollick,&nbsp;Sonia Laín","doi":"10.1186/s40170-020-00218-5","DOIUrl":"https://doi.org/10.1186/s40170-020-00218-5","url":null,"abstract":"<p><p>By providing the necessary building blocks for nucleic acids and precursors for cell membrane synthesis, pyrimidine ribonucleotides are essential for cell growth and proliferation. Therefore, depleting pyrimidine ribonucleotide pools has long been considered as a strategy to reduce cancer cell growth. Here, we review the pharmacological approaches that have been employed to modulate pyrimidine ribonucleotide synthesis and degradation routes and discuss their potential use in cancer therapy. New developments in the treatment of myeloid malignancies with inhibitors of pyrimidine ribonucleotide synthesis justify revisiting the literature as well as discussing whether targeting this metabolic pathway can be effective and sufficiently selective for cancer cells to warrant an acceptable therapeutic index in patients.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"8 ","pages":"12"},"PeriodicalIF":5.9,"publicationDate":"2020-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40170-020-00218-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38462307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of redox homeostasis for combinatorial drug efficacy in <i>K-Ras</i> tumors as revealed by metabolic connectivity profiling.","authors":"Daniela Gaglio,&nbsp;Marcella Bonanomi,&nbsp;Silvia Valtorta,&nbsp;Rohit Bharat,&nbsp;Marilena Ripamonti,&nbsp;Federica Conte,&nbsp;Giulia Fiscon,&nbsp;Nicole Righi,&nbsp;Elisabetta Napodano,&nbsp;Federico Papa,&nbsp;Isabella Raccagni,&nbsp;Seth J Parker,&nbsp;Ingrid Cifola,&nbsp;Tania Camboni,&nbsp;Paola Paci,&nbsp;Anna Maria Colangelo,&nbsp;Marco Vanoni,&nbsp;Christian M Metallo,&nbsp;Rosa Maria Moresco,&nbsp;Lilia Alberghina","doi":"10.1186/s40170-020-00227-4","DOIUrl":"https://doi.org/10.1186/s40170-020-00227-4","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Background: </strong>Rewiring of metabolism induced by oncogenic <i>K-Ras</i> in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways.</p><p><strong>Methods: </strong>We performed mass spectrometric metabolomics analysis in vitro and in vivo experiments to evaluate the efficacy of drugs and identify metabolic connectivity.</p><p><strong>Results: </strong>We show that <i>K-Ras</i>-mutant lung and colon cancer cells exhibit a distinct metabolic rewiring, the latter being more dependent on respiration. Combined treatment with the glutaminase inhibitor CB-839 and the PI3K/aldolase inhibitor NVP-BKM120 more consistently reduces cell growth of tumor xenografts. Maximal growth inhibition correlates with the disruption of redox homeostasis, involving loss of reduced glutathione regeneration, redox cofactors, and a decreased connectivity among metabolites primarily involved in nucleic acid metabolism.</p><p><strong>Conclusions: </strong>Our findings open the way to develop metabolic connectivity profiling as a tool for a selective strategy of combined drug repositioning in precision oncology.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"8 ","pages":"22"},"PeriodicalIF":5.9,"publicationDate":"2020-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40170-020-00227-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38541153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body mass index-associated molecular characteristics involved in tumor immune and metabolic pathways.","authors":"Chao Hu,&nbsp;Xiong Chen,&nbsp;Chengyun Yao,&nbsp;Yu Liu,&nbsp;Haojun Xu,&nbsp;Guoren Zhou,&nbsp;Hongping Xia,&nbsp;Jinglin Xia","doi":"10.1186/s40170-020-00225-6","DOIUrl":"https://doi.org/10.1186/s40170-020-00225-6","url":null,"abstract":"<p><strong>Background: </strong>Overweight or obesity has been evidenced as an important risk factor involved in the incidence, mortality, and therapy response of multiple malignancies. However, the differences between healthy and obesity tumor patients at the molecular and multi-omics levels remain unclear.</p><p><strong>Methods: </strong>Our study performed a comprehensive and multidimensional analysis in fourteen tumor types of The Cancer Genome Atlas (TCGA) and found body mass index (BMI)-related genes in multiple tumor types. Furthermore, we compared composite expression between normal, overweight, and obese patients of each immune cell subpopulation and metabolism gene subset. Statistical significance was calculated via the Kruskal-Wallis rank-sum test.</p><p><strong>Results: </strong>Our analysis revealed that BMI-related genes are enriched in multiple tumor-related biological pathways involved in intracellular signaling, immune response, and metabolism. We also found the different relationships between BMI and different immune cell infiltration and metabolic pathway activity. Importantly, we found that many clinically actionable genes were BMI-affect genes.</p><p><strong>Conclusion: </strong>Overall, our data indicated that BMI-associated molecular characteristics involved in tumor immune and metabolic pathways, which may highlight the clinical importance of considering BMI-associated molecular signatures in cancer precision medicine.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"8 ","pages":"21"},"PeriodicalIF":5.9,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40170-020-00225-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38439376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis.","authors":"Jacqueline Tait-Mulder, Kelly Hodge, David Sumpton, Sara Zanivan, Alexei Vazquez","doi":"10.1186/s40170-020-00228-3","DOIUrl":"10.1186/s40170-020-00228-3","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial serine catabolism to formate induces a metabolic switch to a hypermetabolic state with high rates of glycolysis, purine synthesis and pyrimidine synthesis. While formate is a purine precursor, it is not clear how formate induces pyrimidine synthesis.</p><p><strong>Methods: </strong>Here we combine phospho-proteome and metabolic profiling to determine how formate induces pyrimidine synthesis.</p><p><strong>Results: </strong>We discover that formate induces phosphorylation of carbamoyl phosphate synthetase (CAD), which is known to increase CAD enzymatic activity. Mechanistically, formate induces mechanistic target of rapamycin complex 1 (mTORC1) activity as quantified by phosphorylation of its targets S6, 4E-BP1, S6K1 and CAD. Treatment with the allosteric mTORC1 inhibitor rapamycin abrogates CAD phosphorylation and pyrimidine synthesis induced by formate. Furthermore, we show that the formate-dependent induction of mTOR signalling and CAD phosphorylation is dependent on an increase in purine synthesis.</p><p><strong>Conclusions: </strong>We conclude that formate activates mTORC1 and induces pyrimidine synthesis via the mTORC1-dependent phosphorylation of CAD.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"8 ","pages":"20"},"PeriodicalIF":5.9,"publicationDate":"2020-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38417301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic plasticity imparts erlotinib-resistance in pancreatic cancer by upregulating glucose-6-phosphate dehydrogenase.","authors":"Neha Sharma,&nbsp;Alok Bhushan,&nbsp;Jun He,&nbsp;Gagan Kaushal,&nbsp;Vikas Bhardwaj","doi":"10.1186/s40170-020-00226-5","DOIUrl":"https://doi.org/10.1186/s40170-020-00226-5","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant forms of cancer. Lack of effective treatment options and drug resistance contributes to the low survival among PDAC patients. In this study, we investigated the metabolic alterations in pancreatic cancer cells that do not respond to the EGFR inhibitor erlotinib. We selected erlotinib-resistant pancreatic cancer cells from MiaPaCa2 and AsPC1 cell lines. Metabolic profiling of erlotinib-resistant cells revealed a significant downregulation of glycolytic activity and reduced level of glycolytic metabolites compared to the sensitive cells. The resistant cells displayed elevated expression of the pentose phosphate pathway (PPP) enzymes involved in ROS regulation and nucleotide biosynthesis. The enhanced PPP elevated cellular NADPH/NADP+ ratio and protected the cells from reactive oxygen species (ROS)-induced damage. Inhibition of PPP using 6-aminonicotinamide (6AN) elevated ROS levels, induced G1 cell cycle arrest, and sensitized resistant cells to erlotinib. Genetic studies identified elevated PPP enzyme glucose-6-phosphate dehydrogenase (G6PD) as an important contributor to erlotinib resistance. Mechanistically, our data showed that upregulation of inhibitor of differentiation (ID1) regulates G6PD expression in resistant cells thus contributing to altered metabolic phenotype and reduced response to erlotinib. Together, our results highlight an underlying role of tumor metabolism in PDAC drug response and identify G6PD as a target to overcome drug resistance.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"8 ","pages":"19"},"PeriodicalIF":5.9,"publicationDate":"2020-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40170-020-00226-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38417302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A system for classifying cancers diagnosed in adolescents and young adults","authors":"Ronald D Barr, L. Ries, A. Trama, G. Gatta, E. Steliarova-Foucher, C. Stiller, W. Bleyer","doi":"10.2139/ssrn.3502376","DOIUrl":"https://doi.org/10.2139/ssrn.3502376","url":null,"abstract":"","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"53 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2020-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81481005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}