{"doi":"10.3390/cells10051056","title":"Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation","abstract":"<jats:p>Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. These metabolic alterations include (1) a shift from oxidative phosphorylation to aerobic glycolysis to support the increased need for ATP, (2) increased glutaminolysis for NADPH regeneration, (3) altered flux through the pentose phosphate pathway and the tricarboxylic acid cycle for macromolecule generation, (4) increased lipid uptake, lipogenesis, and cholesterol synthesis, (5) upregulation of one-carbon metabolism for the production of ATP, NADH/NADPH, nucleotides, and glutathione, (6) altered amino acid metabolism, (7) metabolism-based regulation of apoptosis, and (8) the utilization of alternative substrates, such as lactate and acetate. Altered metabolic flux in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, and other regulatory molecules, including non-coding RNAs. Changes to metabolic pathways in cancer are dynamic, exhibit plasticity, and are often dependent on the type of tumor and the tumor microenvironment, leading in a shift of thought from the Warburg Effect and the “reverse Warburg Effect” to metabolic plasticity. Understanding the complex nature of altered flux through these multiple pathways in cancer cells can support the development of new therapies.</jats:p>","journal":"Cells","year":2021,"id":14386,"datarank":6.460068301573869,"base_score":6.391917113392602,"endowment":6.391917113392602,"self_citation_contribution":0.9587875670088905,"citation_network_contribution":5.501280734564978,"self_endowment_contribution":0.9587875670088905,"citer_contribution":5.501280734564978,"corpus_percentile":null,"corpus_rank":null,"citation_count":596,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":25,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":113855,"name":"Bonnie L. Firestein","orcid":"0000-0002-1679-3565","position":1,"is_corresponding":false},{"id":113854,"name":"Chelsea Schiliro","orcid":"0000-0003-1640-9946","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":6.391917113392602,"endowment":6.391917113392602,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33946927","pmcid":"PMC8146072","openalex_id":"https://openalex.org/W3158660301","authors":[],"funders":[],"total_grants":0,"fwci":33.6871,"citation_percentile":0.99907949,"influential_citations":11,"citation_trend":[{"year":2021,"count":24},{"year":2022,"count":59},{"year":2023,"count":128},{"year":2024,"count":160},{"year":2025,"count":173},{"year":2026,"count":51}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4409/10/5/1056/pdf?version=1668414655","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4409/10/5/1056/pdf?version=1668414655","host_type":"GOLD"},{"url":"https://www.mdpi.com/2073-4409/10/5/1056/pdf?version=1668414655","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4409/10/5/1056/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cells10051056","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33946927","host_type":"repository"},{"url":"https://doaj.org/article/7ad0db7b007b408e84ae1d4451783be3","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/cells10051056","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8146072","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8146072","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8146072?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer, Hypoxia, and Metabolism","Metabolism, Diabetes, and Cancer","Cancer, Lipids, and Metabolism","Medicine","Biology","Animals","Apoptosis","Cell Proliferation","Energy Metabolism","Gene Expression Regulation, Neoplastic","Humans","Neoplasms"],"mesh_terms":["Animals","Energy Metabolism","Humans","Neoplasms","Gene Expression Regulation, Neoplastic","Apoptosis","Cell Proliferation"],"keywords":["Reprogramming","Cancer","Cell biology","Cell growth","Cancer cell","Biology","Cancer research","Chemistry","Cell","Biochemistry","Genetics","Oxidative phosphorylation","Pentose phosphate pathway","Warburg Effect","Aerobic Glycolysis","One-carbon Metabolism"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.17693377.v1","title":"Additional file 4 of Glucose starvation suppresses gastric cancer through targeting miR-216a-5p/Farnesyl-Diphosphate Farnesyltransferase 1 axis","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.17693377","title":"Additional file 4 of Glucose starvation suppresses gastric cancer through targeting miR-216a-5p/Farnesyl-Diphosphate Farnesyltransferase 1 axis","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22601548.v1","title":"Additional file 5 of RBX1 regulates PKM alternative splicing to facilitate anaplastic thyroid carcinoma metastasis and aerobic glycolysis by destroying the SMAR1/HDAC6 complex","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22601548","title":"Additional file 5 of RBX1 regulates PKM alternative splicing to facilitate anaplastic thyroid carcinoma metastasis and aerobic glycolysis by destroying the SMAR1/HDAC6 complex","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26562196.v1","title":"Additional file 1 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26562196","title":"Additional file 1 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26642686.v1","title":"Additional file 3 of Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26642686","title":"Additional file 3 of Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.24597541","title":"Additional file 1 of Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.24597749.v1","title":"Additional file 2 of Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.24597541.v1","title":"Additional file 1 of Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.24597749","title":"Additional file 2 of Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26562199.v1","title":"Additional file 2 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562202.v1","title":"Additional file 3 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562208","title":"Additional file 5 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562199","title":"Additional file 2 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562202","title":"Additional file 3 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562214.v1","title":"Additional file 6 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562205","title":"Additional file 4 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562208.v1","title":"Additional file 5 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562214","title":"Additional file 6 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26562205.v1","title":"Additional file 4 of FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.17693374.v1","title":"Additional file 3 of Glucose starvation suppresses gastric cancer through targeting miR-216a-5p/Farnesyl-Diphosphate Farnesyltransferase 1 axis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.17693371","title":"Additional file 2 of Glucose starvation suppresses gastric cancer through targeting miR-216a-5p/Farnesyl-Diphosphate Farnesyltransferase 1 axis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.17693368","title":"Additional file 1 of Glucose starvation suppresses gastric cancer through targeting miR-216a-5p/Farnesyl-Diphosphate Farnesyltransferase 1 axis","publisher":"figshare","resource_type":"Image"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T09:20:33.506147Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}