{"doi":"10.1016/j.cell.2012.10.047","title":"The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism","abstract":"Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of SIRT6 leads to tumor formation without activation of known oncogenes, whereas transformed SIRT6-deficient cells display increased glycolysis and tumor growth, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. By using a conditional SIRT6 allele, we show that SIRT6 deletion in vivo increases the number, size, and aggressiveness of tumors. SIRT6 also functions as a regulator of ribosome metabolism by corepressing MYC transcriptional activity. Lastly, Sirt6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our studies reveal SIRT6 to be a potent tumor suppressor acting to suppress cancer metabolism.","journal":"Cell","year":2012,"id":1996,"datarank":0.9738359752530708,"base_score":6.492239835020471,"endowment":6.492239835020471,"self_citation_contribution":0.9738359752530708,"citation_network_contribution":0.0,"self_endowment_contribution":0.9738359752530708,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":659,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0479,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2012-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23508,"name":"Bernadette M.M. Zwaans","orcid":null,"position":1,"is_corresponding":false},{"id":23509,"name":"Dafne M. Silberman","orcid":"0000-0002-1698-7191","position":2,"is_corresponding":false},{"id":2972,"name":"Madhusudan Gujral","orcid":"0000-0001-5010-4826","position":3,"is_corresponding":false},{"id":855,"name":"Alon Goren","orcid":"0000-0001-5669-9357","position":4,"is_corresponding":false},{"id":23510,"name":"Lei Zhong","orcid":"0000-0002-1901-9698","position":5,"is_corresponding":false},{"id":854,"name":"Oren Ram","orcid":"0000-0001-6341-5252","position":6,"is_corresponding":false},{"id":23511,"name":"Jessica Truelove","orcid":null,"position":7,"is_corresponding":false},{"id":23512,"name":"Alexander R. Guimaraes","orcid":null,"position":8,"is_corresponding":false},{"id":23513,"name":"Debra Toiber","orcid":"0000-0002-1465-0130","position":9,"is_corresponding":false},{"id":23514,"name":"Claudia Cosentino","orcid":"0000-0002-9817-5030","position":10,"is_corresponding":false},{"id":23515,"name":"Joel K. Greenson","orcid":null,"position":11,"is_corresponding":false},{"id":23516,"name":"Alasdair I. MacDonald","orcid":null,"position":12,"is_corresponding":false},{"id":23517,"name":"Liane McGlynn","orcid":null,"position":13,"is_corresponding":false},{"id":23518,"name":"Fraser Maxwell","orcid":null,"position":14,"is_corresponding":false},{"id":23519,"name":"Joanne Edwards","orcid":"0000-0002-7192-6906","position":15,"is_corresponding":false},{"id":23520,"name":"Sofia Giacosa","orcid":null,"position":16,"is_corresponding":false},{"id":23521,"name":"Ernesto Guccione","orcid":"0000-0001-7764-5307","position":17,"is_corresponding":false},{"id":23522,"name":"Ralph Weissleder","orcid":"0000-0003-0828-4143","position":18,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":20,"is_corresponding":false},{"id":23523,"name":"Paul G. Shiels","orcid":"0000-0002-7577-9843","position":21,"is_corresponding":false},{"id":23524,"name":"David B. Lombard","orcid":"0000-0002-4292-0185","position":22,"is_corresponding":false},{"id":23525,"name":"Raul Mostoslavsky","orcid":null,"position":23,"is_corresponding":false},{"id":23526,"name":"Bernadette Zwaans","orcid":"0000-0002-4717-5751","position":24,"is_corresponding":false},{"id":23527,"name":"Alexander R. Guimarães","orcid":"0000-0003-4601-9340","position":25,"is_corresponding":false},{"id":23528,"name":"Liane M. McGlynn","orcid":null,"position":26,"is_corresponding":false},{"id":42925,"name":"Louis Philip Benoit Bouvrette","orcid":"0000-0003-2726-5669","position":27,"is_corresponding":false},{"id":23529,"name":"Raúl Mostoslavsky","orcid":"0000-0002-7740-5212","position":28,"is_corresponding":false},{"id":23507,"name":"Carlos Sebastián","orcid":"0000-0001-6623-8028","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}