{"doi":"10.1101/2022.09.10.507413","title":"The glutathione S-transferase Gstt1 is a robust driver of survival and dissemination in metastases","abstract":"ABSTRACT Identifying adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (PDA), where the majority of patients present with metastatic lesions at the time of diagnosis. A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1 , a member of the glutathione S-transferase superfamily, as uniquely required for metastasis and dissemination however dispensable for primary tumor growth. Gstt1 is expressed in early disseminated tumor cells (DTCs), is retained within a subpopulation of slow-cycling cells within established metastases and its inhibition led to a regression of macrometastatic lesions. This distinct Gstt1 high population is highly metastatic and retains slow-cycling phenotypes, EMT features, and DTC characteristics compared to the Gstt1 low population. Mechanistic studies indicate that in this subset of cells, Gstt1 maintains metastases by binding to and modifying intracellular fibronectin, regulating Fibronectin secretion from cancer cells and deposition into the metastatic microenvironment. We identified Gstt1 as a novel mediator of metastasis, highlighting the importance of metastatic heterogeneity and its influence on the metastatic tumor microenvironment.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":311302,"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":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":666244,"name":"Ruben Boon","orcid":"0000-0002-9355-674X","position":1,"is_corresponding":false},{"id":1007533,"name":"Hyo Min Cho","orcid":"0000-0002-4862-220X","position":2,"is_corresponding":false},{"id":564806,"name":"Tiziano Bernasocchi","orcid":"0000-0002-7130-5317","position":3,"is_corresponding":false},{"id":500244,"name":"Lai Ping Wong","orcid":null,"position":4,"is_corresponding":false},{"id":260527,"name":"Murat Çetinbaş","orcid":"0000-0002-7516-8225","position":5,"is_corresponding":false},{"id":863764,"name":"Elizabeth R. Haggerty","orcid":null,"position":6,"is_corresponding":false},{"id":1007534,"name":"Irene Mitsiades","orcid":"0000-0002-9734-6803","position":7,"is_corresponding":false},{"id":271226,"name":"Gregory R. Wojtkiewicz","orcid":"0000-0002-3148-8411","position":8,"is_corresponding":false},{"id":614911,"name":"Daniel E. McLoughlin","orcid":"0000-0002-3697-9623","position":9,"is_corresponding":false},{"id":432432,"name":"Sita Kugel","orcid":"0000-0001-7202-187X","position":10,"is_corresponding":false},{"id":267579,"name":"Esther Rheinbay","orcid":"0000-0002-5566-6729","position":11,"is_corresponding":false},{"id":260528,"name":"Ruslan I. Sadreyev","orcid":"0000-0002-4240-5466","position":12,"is_corresponding":false},{"id":33176,"name":"Dejan Juric","orcid":"0000-0003-2983-7704","position":13,"is_corresponding":false},{"id":23529,"name":"Raúl Mostoslavsky","orcid":"0000-0002-7740-5212","position":14,"is_corresponding":false},{"id":666241,"name":"Christina M. Ferrer","orcid":"0009-0006-8651-9154","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:33:28.480200Z","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":[]}