{"doi":"10.1101/2020.04.29.068577","title":"Tumor -Associated MUC1 Regulates TGF-β Signaling and Function in Pancreatic Ductal Adenocarcinoma","abstract":"Abstract Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human cancers. Transforming Growth Factor Beta (TGF-β) is a cytokine that switches from a tumor-suppressor to a tumor promoter throughout tumor development, by a yet unknown mechanism. Tumor associated MUC1 (tMUC1) is aberrantly glycosylated and overexpressed in >80% of PDAs and is associated with poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) interacts with other oncogenic proteins promoting tumor progression and metastasis. We hypothesize that tMUC1 levels regulate TGF-β functions in PDA in vitro and in vivo . We report that high-tMUC1 expression positively correlates to TGF-βRII and negatively to TGF-βRI receptors. In response to TGF-β1, high tMUC1 expressing PDA cells undergo c-Src phosphorylation, and activation of the Erk/MAPK pathway; while low tMUC1 expressing cells activate the Smad2/3 pathway, enhancing cell death. Correspondingly, mice bearing tMUC1-high tumors responded to TGF-β1 neutralizing antibody in vivo showing significantly retarded tumor growth. Analysis of clinical data from TCGA revealed significant alterations in gene-gene correlations in the TGF-β pathway in tMUC1 high versus tMUC1 low samples. This study deepens our understanding of tMUC1-regulated TGF-β’s paradoxical function in PDA and establishes tMUC1 as a potential biomarker to predict response to TGF-β-targeted therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126645,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":575193,"name":"Sritama Nath","orcid":null,"position":1,"is_corresponding":false},{"id":568802,"name":"Mukulika Bose","orcid":"0000-0002-2347-7413","position":2,"is_corresponding":false},{"id":574516,"name":"Alexa Sanders","orcid":"0000-0001-7486-1194","position":3,"is_corresponding":false},{"id":574517,"name":"Cory Brouwer","orcid":"0000-0003-4136-3249","position":4,"is_corresponding":false},{"id":444785,"name":"Nitika Nitika","orcid":null,"position":5,"is_corresponding":false},{"id":574518,"name":"Ru Zhou","orcid":"0000-0002-3502-9861","position":6,"is_corresponding":false},{"id":574519,"name":"Mahboubeh Yazdanifar","orcid":"0000-0003-1884-3383","position":7,"is_corresponding":false},{"id":574520,"name":"Mohammad Ahmad","orcid":"0000-0003-1228-4445","position":8,"is_corresponding":false},{"id":462428,"name":"Shu-ta Wu","orcid":null,"position":9,"is_corresponding":false},{"id":444005,"name":"Andrew W. Truman","orcid":"0000-0002-6409-3723","position":10,"is_corresponding":false},{"id":461051,"name":"Pinku Mukherjee","orcid":"0000-0002-6782-3576","position":11,"is_corresponding":false},{"id":575192,"name":"Priyanka Grover","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}