{"doi":"10.1158/1541-7786.c.6545003.v1","title":"Data from AXL Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer","abstract":"<div>Abstract<p>Pancreatic ductal adenocarcinoma (PDA), a leading cause of cancer-related death in the United States, has a high metastatic rate, and is associated with persistent immune suppression. AXL, a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family, is a driver of metastasis and immune suppression in multiple cancer types. Here we use single-cell RNA-sequencing to reveal that AXL is expressed highly in tumor cells that have a mesenchymal-like phenotype and that AXL expression correlates with classic markers of epithelial-to-mesenchymal transition. We demonstrate that AXL deficiency extends survival, reduces primary and metastatic burden, and enhances sensitivity to gemcitabine in an autochthonous model of PDA. PDA in AXL-deficient mice displayed a more differentiated histology, higher nucleoside transporter expression, and a more active immune microenvironment compared with PDA in wild-type mice. Finally, we demonstrate that AXL-positive poorly differentiated tumor cells are critical for PDA progression and metastasis, emphasizing the potential of AXL as a therapeutic target in PDA.</p>Implications:<p>These studies implicate AXL as a marker of undifferentiated PDA cells and a target for therapy.</p></div>","journal":null,"year":2023,"id":406075,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"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":564799,"name":"Natalie Z. Phinney","orcid":"0000-0001-5366-0510","position":1,"is_corresponding":false},{"id":513304,"name":"Huocong Huang","orcid":"0000-0002-6345-4566","position":2,"is_corresponding":false},{"id":251123,"name":"Zhaoning Wang","orcid":"0000-0002-0290-4746","position":3,"is_corresponding":false},{"id":582251,"name":"Jill M. Westcott","orcid":"0000-0003-4403-2090","position":4,"is_corresponding":false},{"id":564798,"name":"Jason E. Toombs","orcid":"0000-0002-9264-3761","position":5,"is_corresponding":false},{"id":564800,"name":"Yuqing Zhang","orcid":"0000-0002-6318-3575","position":6,"is_corresponding":false},{"id":107742,"name":"Muhammad Shaalan Beg","orcid":"0000-0002-3754-6627","position":7,"is_corresponding":false},{"id":532242,"name":"Thomas M. Wilkie","orcid":"0000-0002-9357-637X","position":8,"is_corresponding":false},{"id":88845,"name":"James B. Lorens","orcid":"0000-0002-6782-3349","position":9,"is_corresponding":false},{"id":286302,"name":"Rolf A. Brekken","orcid":"0000-0003-2704-2377","position":10,"is_corresponding":false},{"id":564797,"name":"Wenting Du","orcid":"0000-0001-6765-0129","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:59.152593Z","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":[]}