{"doi":"10.1016/j.celrep.2023.113434","title":"SERPINB3-MYC axis induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer","abstract":"Pancreatic ductal adenocarcinoma (PDAC) exhibits distinct molecular subtypes: classical/progenitor and basal-like/squamous. Our study aimed to identify genes contributing to the development of the basal-like/squamous subtype, known for its aggressiveness. Transcriptome analyses revealed consistent upregulation of SERPINB3 in basal-like/squamous PDAC, correlating with reduced patient survival. SERPINB3 transgene expression in PDAC cells enhanced in vitro invasion and promoted lung metastasis in a mouse PDAC xenograft model. Metabolome analyses unveiled a metabolic signature linked to both SERPINB3 and the basal-like/squamous subtype, characterized by heightened carnitine/acylcarnitine and amino acid metabolism, associated with poor prognosis in patients with PDAC and elevated cellular invasiveness. Further analysis uncovered that SERPINB3 inhibited the cysteine protease calpain, a key enzyme in the MYC degradation pathway, and drove basal-like/squamous subtype and associated metabolic reprogramming through MYC activation. Our findings indicate that the SERPINB3-MYC axis induces the basal-like/squamous subtype, proposing SERPINB3 as a potential diagnostic and therapeutic target for this variant.","journal":"Cell Reports","year":2023,"id":323520,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":276003,"name":"Wei Tang","orcid":"0000-0002-7089-4391","position":1,"is_corresponding":false},{"id":210845,"name":"Huaitian Liu","orcid":"0000-0002-7791-1502","position":2,"is_corresponding":false},{"id":862723,"name":"Shouhui Yang","orcid":null,"position":3,"is_corresponding":false},{"id":210848,"name":"Tiffany H. Dorsey","orcid":"0009-0003-1334-0098","position":4,"is_corresponding":false},{"id":862167,"name":"Helen Cawley","orcid":"0009-0004-0967-2011","position":5,"is_corresponding":false},{"id":1038784,"name":"Paloma Moreno","orcid":null,"position":6,"is_corresponding":false},{"id":260578,"name":"Raj Chari","orcid":"0000-0002-2216-313X","position":7,"is_corresponding":false},{"id":1038785,"name":"Mary Guest","orcid":null,"position":8,"is_corresponding":false},{"id":862165,"name":"Azadeh Azizian","orcid":"0000-0003-4270-5706","position":9,"is_corresponding":false},{"id":862166,"name":"Jochen Gaedcke","orcid":"0000-0002-6130-5874","position":10,"is_corresponding":false},{"id":912498,"name":"Michael Ghadimi","orcid":"0000-0001-8208-1526","position":11,"is_corresponding":false},{"id":862168,"name":"Nader Hanna","orcid":"0000-0001-5755-5910","position":12,"is_corresponding":false},{"id":130771,"name":"Stefan Ambs","orcid":"0000-0001-7651-9309","position":13,"is_corresponding":false},{"id":276011,"name":"S. Perwez Hussain","orcid":"0000-0002-2294-522X","position":14,"is_corresponding":false},{"id":857717,"name":"Yuuki Ohara","orcid":"0000-0002-9171-4724","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T01:07:52.377944Z","pmid":"37980563","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":[]}