Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types
Malignant cells are commonly characterised by being capable of invading tissue, growing self-sufficiently and uncontrollably, being insensitive to apoptosis induction and controlling their environment, for example inducing angiogenesis. Amongst them, a subpopulation of cancer cells, called cancer st...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.723798/full |
| _version_ | 1819099428956405760 |
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| author | Andrea Chisari Irene Golán Sabrina Campisano Caroline Gélabert Aristidis Moustakas Patricia Sancho Laia Caja |
| author_facet | Andrea Chisari Irene Golán Sabrina Campisano Caroline Gélabert Aristidis Moustakas Patricia Sancho Laia Caja |
| author_sort | Andrea Chisari |
| collection | DOAJ |
| description | Malignant cells are commonly characterised by being capable of invading tissue, growing self-sufficiently and uncontrollably, being insensitive to apoptosis induction and controlling their environment, for example inducing angiogenesis. Amongst them, a subpopulation of cancer cells, called cancer stem cells (CSCs) shows sustained replicative potential, tumor-initiating properties and chemoresistance. These characteristics make CSCs responsible for therapy resistance, tumor relapse and growth in distant organs, causing metastatic dissemination. For these reasons, eliminating CSCs is necessary in order to achieve long-term survival of cancer patients. New insights in cancer metabolism have revealed that cellular metabolism in tumors is highly heterogeneous and that CSCs show specific metabolic traits supporting their unique functionality. Indeed, CSCs adapt differently to the deprivation of specific nutrients that represent potentially targetable vulnerabilities. This review focuses on three of the most aggressive tumor types: pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC) and glioblastoma (GBM). The aim is to prove whether CSCs from different tumour types share common metabolic requirements and responses to nutrient starvation, by outlining the diverse roles of glucose and amino acids within tumour cells and in the tumour microenvironment, as well as the consequences of their deprivation. Beyond their role in biosynthesis, they serve as energy sources and help maintain redox balance. In addition, glucose and amino acid derivatives contribute to immune responses linked to tumourigenesis and metastasis. Furthermore, potential metabolic liabilities are identified and discussed as targets for therapeutic intervention. |
| first_indexed | 2024-12-22T00:46:44Z |
| format | Article |
| id | doaj.art-3cf403a8496b477b991635169e8bfb38 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T00:46:44Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-3cf403a8496b477b991635169e8bfb382022-12-21T18:44:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.723798723798Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer TypesAndrea Chisari0Irene Golán1Sabrina Campisano2Caroline Gélabert3Aristidis Moustakas4Patricia Sancho5Laia Caja6Department of Chemistry, School of Sciences, National University of Mar del Plata, Mar del Plata, ArgentinaDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, SwedenDepartment of Chemistry, School of Sciences, National University of Mar del Plata, Mar del Plata, ArgentinaDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, SwedenTranslational Research Unit, Hospital Universitario Miguel Servet, IIS Aragon, Zaragoza, SpainDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, SwedenMalignant cells are commonly characterised by being capable of invading tissue, growing self-sufficiently and uncontrollably, being insensitive to apoptosis induction and controlling their environment, for example inducing angiogenesis. Amongst them, a subpopulation of cancer cells, called cancer stem cells (CSCs) shows sustained replicative potential, tumor-initiating properties and chemoresistance. These characteristics make CSCs responsible for therapy resistance, tumor relapse and growth in distant organs, causing metastatic dissemination. For these reasons, eliminating CSCs is necessary in order to achieve long-term survival of cancer patients. New insights in cancer metabolism have revealed that cellular metabolism in tumors is highly heterogeneous and that CSCs show specific metabolic traits supporting their unique functionality. Indeed, CSCs adapt differently to the deprivation of specific nutrients that represent potentially targetable vulnerabilities. This review focuses on three of the most aggressive tumor types: pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC) and glioblastoma (GBM). The aim is to prove whether CSCs from different tumour types share common metabolic requirements and responses to nutrient starvation, by outlining the diverse roles of glucose and amino acids within tumour cells and in the tumour microenvironment, as well as the consequences of their deprivation. Beyond their role in biosynthesis, they serve as energy sources and help maintain redox balance. In addition, glucose and amino acid derivatives contribute to immune responses linked to tumourigenesis and metastasis. Furthermore, potential metabolic liabilities are identified and discussed as targets for therapeutic intervention.https://www.frontiersin.org/articles/10.3389/fphar.2021.723798/fullglucoseamino acidPDAC-pancreatic ductal adenocarcinomaGBM-glioblastoma multiformeHCC-hepatocellular carcinomacancer stem cell (CSC) |
| spellingShingle | Andrea Chisari Irene Golán Sabrina Campisano Caroline Gélabert Aristidis Moustakas Patricia Sancho Laia Caja Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types Frontiers in Pharmacology glucose amino acid PDAC-pancreatic ductal adenocarcinoma GBM-glioblastoma multiforme HCC-hepatocellular carcinoma cancer stem cell (CSC) |
| title | Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types |
| title_full | Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types |
| title_fullStr | Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types |
| title_full_unstemmed | Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types |
| title_short | Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types |
| title_sort | glucose and amino acid metabolic dependencies linked to stemness and metastasis in different aggressive cancer types |
| topic | glucose amino acid PDAC-pancreatic ductal adenocarcinoma GBM-glioblastoma multiforme HCC-hepatocellular carcinoma cancer stem cell (CSC) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.723798/full |
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