{"doi":"10.1016/j.cell.2021.10.001","title":"Glycogen accumulation and phase separation drives liver tumor initiation","abstract":null,"journal":"Cell","year":2021,"id":672107,"datarank":0.8657161684695025,"base_score":5.771441123130016,"endowment":5.771441123130016,"self_citation_contribution":0.8657161684695025,"citation_network_contribution":0.0,"self_endowment_contribution":0.8657161684695025,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":320,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1396709,"name":"Jiaxin Li","orcid":"0009-0008-1902-6784","position":1,"is_corresponding":false},{"id":1755955,"name":"Weiji Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":1717407,"name":"Chen Xiao","orcid":null,"position":3,"is_corresponding":false},{"id":32126,"name":"Shihao Zhang","orcid":"0000-0003-2439-4078","position":4,"is_corresponding":false},{"id":1755956,"name":"Cheng Nian","orcid":null,"position":5,"is_corresponding":false},{"id":1431413,"name":"Junhong Li","orcid":"0000-0002-4864-0897","position":6,"is_corresponding":false},{"id":1755957,"name":"Dongxue Su","orcid":null,"position":7,"is_corresponding":false},{"id":72466,"name":"Lihong Chen","orcid":"0000-0001-6370-1865","position":8,"is_corresponding":false},{"id":586057,"name":"Qian Zhao","orcid":"0000-0002-4017-465X","position":9,"is_corresponding":false},{"id":430718,"name":"Hui Shao","orcid":"0000-0001-7566-6921","position":10,"is_corresponding":false},{"id":1455547,"name":"Hao Zhao","orcid":"0000-0001-7776-1201","position":11,"is_corresponding":false},{"id":737407,"name":"Qinghua Chen","orcid":"0009-0004-8648-0099","position":12,"is_corresponding":false},{"id":693685,"name":"Yuxi Li","orcid":"0000-0003-0947-4731","position":13,"is_corresponding":false},{"id":328689,"name":"Jing Geng","orcid":"0000-0003-3432-1008","position":14,"is_corresponding":false},{"id":1755958,"name":"Lixin Hong","orcid":null,"position":15,"is_corresponding":false},{"id":335283,"name":"Shuhai Lin","orcid":"0000-0002-4782-5320","position":16,"is_corresponding":false},{"id":256212,"name":"Qiao Wu","orcid":"0000-0001-6206-1659","position":17,"is_corresponding":false},{"id":153339,"name":"Xianming Deng","orcid":null,"position":18,"is_corresponding":false},{"id":1604111,"name":"Rongqin Ke","orcid":"0000-0002-9868-3713","position":19,"is_corresponding":false},{"id":630618,"name":"Jin Ding","orcid":"0000-0003-3585-6063","position":20,"is_corresponding":false},{"id":246168,"name":"Randy L. Johnson","orcid":"0000-0003-4549-3593","position":21,"is_corresponding":false},{"id":1215927,"name":"Xiaolong Liu","orcid":"0000-0001-6818-5417","position":22,"is_corresponding":false},{"id":568407,"name":"Lanfen Chen","orcid":"0000-0002-9413-1284","position":23,"is_corresponding":false},{"id":1398193,"name":"Dawang Zhou","orcid":"0000-0002-9053-5249","position":24,"is_corresponding":false},{"id":1755954,"name":"Qingxu Liu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Glycogen accumulation and phase separation drives liver tumor initiation","abstract":"Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex and consequently sequesters Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme-liver glycogen phosphorylase (PYGL) deficiency in both human and mice results in glycogen storage disease along with liver enlargement and tumorigenesis in a Yap-dependent manner. Consistently, elimination of glycogen accumulation abrogates liver growth and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that cancer-initiating cells adapt a glycogen storing mode, which blocks Hippo signaling through glycogen phase separation to augment tumor incidence.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34678143","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"National Key Research and Development Program of China","grant_id":"2017YFA0504502","title":null},{"funder_name":"Fundamental Research Funds for the Central Universities","grant_id":"20720180047","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81902797","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"B21023","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31625010","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"U1905208","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81925016","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82021003","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81871973","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81830046","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81790254","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31770927","title":null},{"funder_name":"Higher Education Discipline Innovation Project","grant_id":"","title":null},{"funder_name":"Xiamen University","grant_id":"","title":null}],"total_grants":14,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0092867421011752?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867421011752?httpAccept=text/plain","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Liver","Cell Line","Animals","Mice, Inbred C57BL","Mice, Knockout","Humans","Mice","Liver Neoplasms","Precancerous Conditions","Disease Models, Animal","Glycogen","Glucose-6-Phosphatase","Glycogen Phosphorylase","Hepatocyte Growth Factor","Proto-Oncogene Proteins","Neoplasm Staging","Down-Regulation","Gene Expression Regulation, Neoplastic","Phase Transition","Adult","Aged","Aged, 80 and over","Middle Aged","Female","Male","Protein Tyrosine Phosphatases, Non-Receptor","Carcinogenesis","Hippo Signaling Pathway","Serine-Threonine Kinase 3","YAP-Signaling Proteins","Hippo Kinases"],"keywords":["Liver cancer","Phase separation","Hippo Signaling","Cancer Initiation","Mst1","Glycogen Storage","Mst2"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T06:32:37.889181Z","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":[]}