{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:26:15Z","timestamp":1791473175449,"version":"4.3.4"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"8","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beatson Advanced Imaging Resource","award":["SCR_023875"],"award-info":[{"award-number":["SCR_023875"]}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A18277"],"award-info":[{"award-number":["A18277"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A28291"],"award-info":[{"award-number":["A28291"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A23982"],"award-info":[{"award-number":["A23982"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A29799"],"award-info":[{"award-number":["A29799"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["PRCBTP-May24\/100005"],"award-info":[{"award-number":["PRCBTP-May24\/100005"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C596\/A18076"],"award-info":[{"award-number":["C596\/A18076"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C596\/A17196"],"award-info":[{"award-number":["C596\/A17196"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A31287"],"award-info":[{"award-number":["A31287"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009794","name":"Breast Cancer Now","doi-asserted-by":"publisher","award":["2019NovPR1268"],"award-info":[{"award-number":["2019NovPR1268"]}],"id":[{"id":"10.13039\/100009794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P01058X\/1"],"award-info":[{"award-number":["MR\/P01058X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009795","name":"Pancreatic Cancer UK Research Innovation","doi-asserted-by":"publisher","award":["2021RIF_22_Voorde"],"award-info":[{"award-number":["2021RIF_22_Voorde"]}],"id":[{"id":"10.13039\/100009795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["318046"],"award-info":[{"award-number":["318046"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,4]]},"abstract":"<jats:p>Altered cellular metabolism has been associated with the acquisition of invasive phenotypes during metastasis. To study this, we combined a genetically engineered mouse model of mammary carcinoma with syngeneic transplantation and primary tumor resection to generate isogenic cells from primary tumors and their corresponding lung micrometastases. Metabolic analyses indicated that micrometastatic cells increase proline production at the expense of glutathione synthesis, leading to a reduction in total glutathione levels. Micrometastatic cells also have altered sphingomyelin metabolism, leading to increased intracellular levels of specific ceramides. The combination of these metabolic adaptations alters extracellular vesicle (EV) production to render the microenvironment more permissive for invasion. Indeed, micrometastatic cells shut down Rab27-dependent production of EVs and, instead, switch on neutral sphingomyelinase-2 (nSM2)-dependent EV release. EVs released in an nSM2-dependent manner from micrometastatic cells, in turn, influence the ability of fibroblasts to deposit extracellular matrix, which promotes cancer cell invasiveness. These data provide evidence that metabolic rewiring drives invasive processes in metastasis by influencing EV release.<\/jats:p>","DOI":"10.1083\/jcb.202405061","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T02:21:04Z","timestamp":1746584464000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments"],"prefix":"10.1083","volume":"224","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-4677","authenticated-orcid":true,"given":"Michalis","family":"Gounis","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7068-3391","authenticated-orcid":true,"given":"America V.","family":"Campos","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-9332","authenticated-orcid":true,"given":"Engy","family":"Shokry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3173-5074","authenticated-orcid":true,"given":"Louise","family":"Mitchell","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-8556","authenticated-orcid":true,"given":"Ruhi","family":"Deshmukh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-8637","authenticated-orcid":true,"given":"Emmanuel","family":"Dornier","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0652-4207","authenticated-orcid":true,"given":"Nicholas","family":"Rooney","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1681-8216","authenticated-orcid":true,"given":"Sandeep","family":"Dhayade","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4355-1369","authenticated-orcid":true,"given":"Luis","family":"Pardo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5246-3955","authenticated-orcid":true,"given":"Madeleine","family":"Moore","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5344-0083","authenticated-orcid":true,"given":"David","family":"Novo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Mowat","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00n3w3b69","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Strathclyde 3 Department of Pure and Applied Chemistry, Thomas Graham Building, , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-8272","authenticated-orcid":true,"given":"Craig","family":"Jamieson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00n3w3b69","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Strathclyde 3 Department of Pure and Applied Chemistry, Thomas Graham Building, , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3398-0960","authenticated-orcid":true,"given":"Emily","family":"Kay","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9880-9099","authenticated-orcid":true,"given":"Sara","family":"Zanivan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0953-4709","authenticated-orcid":true,"given":"Nikki R.","family":"Paul","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9960-2340","authenticated-orcid":true,"given":"Claire","family":"Mitchell","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8085-2160","authenticated-orcid":true,"given":"Colin","family":"Nixon","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4295-8885","authenticated-orcid":true,"given":"Iain","family":"Macpherson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-8683","authenticated-orcid":true,"given":"Saverio","family":"Tardito","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical University of Vienna, Center for Cancer Research and Comprehensive Cancer Center 4 , Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-4079","authenticated-orcid":true,"given":"David","family":"Sumpton","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9304-439X","authenticated-orcid":true,"given":"Karen","family":"Blyth","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-3014","authenticated-orcid":true,"given":"Jim C.","family":"Norman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-1609","authenticated-orcid":true,"given":"Cassie J.","family":"Clarke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03pv69j64","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Research UK Scotland Institute 1 , Glasgow,","place":["UK"]},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer Sciences, University of Glasgow 2 , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"2025060909204987000_bib1","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nrc2256","article-title":"Models, mechanisms and clinical evidence for cancer dormancy","volume":"7","author":"Aguirre-Ghiso","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"2025060909204987000_bib2","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s10585-011-9405-9","article-title":"Migration of MDA-MB-231 breast cancer cells depends on the availability of exogenous lipids and cholesterol esterification","volume":"28","author":"Antalis","year":"2011","journal-title":"Clin. Exp. Metastasis"},{"key":"2025060909204987000_bib3","doi-asserted-by":"publisher","first-page":"107683","DOI":"10.1016\/j.pharmthera.2020.107683","article-title":"Extracellular vesicles in hepatology: Physiological role, involvement in pathogenesis, and therapeutic opportunities","volume":"218","author":"Azparren-Angulo","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"2025060909204987000_bib4","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1083\/jcb.201804161","article-title":"Glutathione metabolism in cancer progression and treatment resistance","volume":"217","author":"Bansal","year":"2018","journal-title":"J. Cell Biol."},{"key":"2025060909204987000_bib5","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1083\/jcb.200610076","article-title":"Syndecan-4-dependent Rac1 regulation determines directional migration in response to the extracellular matrix","volume":"177","author":"Bass","year":"2007","journal-title":"J. Cell Biol."},{"key":"2025060909204987000_bib6","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1158\/1055-9965.EPI-21-1023","article-title":"Plasma metabolomics and breast cancer risk over 20 Years of follow-up among postmenopausal women in the nurses\u2019 health study","volume":"31","author":"Brantley","year":"2022","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"2025060909204987000_bib7","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism","volume":"11","author":"Cairns","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"2025060909204987000_bib8","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1038\/s41418-021-00773-4","article-title":"Breast cancer dependence on MCL-1 is due to its canonical anti-apoptotic function","volume":"28","author":"Campbell","year":"2021","journal-title":"Cell Death Differ."},{"key":"2025060909204987000_bib9","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.celrep.2016.09.042","article-title":"Breast cancer-derived lung metastases show increased pyruvate carboxylase-dependent anaplerosis","volume":"17","author":"Christen","year":"2016","journal-title":"Cell Rep."},{"key":"2025060909204987000_bib10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1385\/1-59259-860-9:079","article-title":"Cell migration analyses within fibroblast-derived 3-D matrices","volume":"294","author":"Cukierman","year":"2005","journal-title":"Methods Mol. Biol."},{"key":"2025060909204987000_bib11","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1038\/s41467-017-02101-2","article-title":"Glutaminolysis drives membrane trafficking to promote invasiveness of breast cancer cells","volume":"8","author":"Dornier","year":"2017","journal-title":"Nat. Commun."},{"key":"2025060909204987000_bib12","doi-asserted-by":"publisher","first-page":"15267","DOI":"10.1038\/ncomms15267","article-title":"Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells","volume":"8","author":"Elia","year":"2017","journal-title":"Nat. Commun."},{"key":"2025060909204987000_bib13","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41586-019-0977-x","article-title":"Breast cancer cells rely on environmental pyruvate to shape the metastatic niche","volume":"568","author":"Elia","year":"2019","journal-title":"Nature"},{"key":"2025060909204987000_bib14","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"2025060909204987000_bib15","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1038\/nprot.2013.095","article-title":"Analysis of GSH and GSSG after derivatization with N-ethylmaleimide","volume":"8","author":"Giustarini","year":"2013","journal-title":"Nat. Protoc."},{"key":"2025060909204987000_bib16","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1128\/mcb.12.3.954-961.1992","article-title":"Induction of mammary tumors by expression of polyomavirus middle T oncogene: A transgenic mouse model for metastatic disease","volume":"12","author":"Guy","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"2025060909204987000_bib17","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ccell.2014.11.019","article-title":"Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression","volume":"27","author":"Harris","year":"2015","journal-title":"Cancer Cell"},{"key":"2025060909204987000_bib18","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.cels.2018.03.011","article-title":"LipiDex: An integrated software package for high-confidence lipid identification","volume":"6","author":"Hutchins","year":"2018","journal-title":"Cell Syst."},{"key":"2025060909204987000_bib19","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.ccell.2019.08.003","article-title":"Epithelial NOTCH signaling rewires the tumor microenvironment of colorectal cancer to drive poor-prognosis subtypes and metastasis","volume":"36","author":"Jackstadt","year":"2019","journal-title":"Cancer Cell"},{"key":"2025060909204987000_bib20","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/nrc2618","article-title":"Microenvironmental regulation of metastasis","volume":"9","author":"Joyce","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"2025060909204987000_bib21","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/978-1-0716-3052-5_22","article-title":"Transwell in vitro cell migration and invasion assays","volume":"2644","author":"Justus","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"2025060909204987000_bib22","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s42255-022-00582-0","article-title":"Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix","volume":"4","author":"Kay","year":"2022","journal-title":"Nat. Metab."},{"key":"2025060909204987000_bib23","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1200\/JCO.2009.25.9820","article-title":"Metastatic behavior of breast cancer subtypes","volume":"28","author":"Kennecke","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"2025060909204987000_bib24","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40880-018-0288-x","article-title":"Amino acid transporter SLC7A11\/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer","volume":"38","author":"Koppula","year":"2018","journal-title":"Cancer Commun. (Lond.)"},{"key":"2025060909204987000_bib25","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s13238-020-00789-5","article-title":"Cystine transporter SLC7A11\/xCT in cancer: Ferroptosis, nutrient dependency, and cancer therapy","volume":"12","author":"Koppula","year":"2021","journal-title":"Protein Cell"},{"key":"2025060909204987000_bib26","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.cmet.2019.07.014","article-title":"Cell clustering promotes a metabolic switch that supports metastatic colonization","volume":"30","author":"Labuschagne","year":"2019","journal-title":"Cell Metab."},{"key":"2025060909204987000_bib27","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.cell.2016.11.037","article-title":"Emerging biological principles of metastasis","volume":"168","author":"Lambert","year":"2017","journal-title":"Cell"},{"key":"2025060909204987000_bib28","doi-asserted-by":"publisher","first-page":"308re8","DOI":"10.1126\/scitranslmed.aad3740","article-title":"Antioxidants can increase melanoma metastasis in mice","volume":"7","author":"Le Gal","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"2025060909204987000_bib29","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/s41598-019-57068-5","article-title":"Metabolomics-based discovery of molecular signatures for triple negative breast cancer in asian female population","volume":"10","author":"Li","year":"2020","journal-title":"Sci. Rep."},{"key":"2025060909204987000_bib30","doi-asserted-by":"publisher","first-page":"736837","DOI":"10.1155\/2012\/736837","article-title":"Glutathione homeostasis and functions: Potential targets for medical interventions","volume":"2012","author":"Lushchak","year":"2012","journal-title":"J. Amino Acids"},{"key":"2025060909204987000_bib31","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/S0002-9440(10)65628-3","article-title":"Multistep nature of metastatic inefficiency: Dormancy of solitary cells after successful extravasation and limited survival of early micrometastases","volume":"153","author":"Luzzi","year":"1998","journal-title":"Am. J. Pathol."},{"key":"2025060909204987000_bib32","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/s43018-023-00721-w","article-title":"Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma","volume":"5","author":"Mahmood","year":"2024","journal-title":"Nat. Cancer"},{"key":"2025060909204987000_bib33","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1016\/j.bmcl.2019.07.047","article-title":"A fragment-like approach to PYCR1 inhibition","volume":"29","author":"Milne","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2025060909204987000_bib34","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nature03799","article-title":"Genes that mediate breast cancer metastasis to lung","volume":"436","author":"Minn","year":"2005","journal-title":"Nature"},{"key":"2025060909204987000_bib35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024143","article-title":"Plasma free amino acid profiling of five types of cancer patients and its application for early detection","volume":"6","author":"Miyagi","year":"2011","journal-title":"PLoS One"},{"key":"2025060909204987000_bib36","doi-asserted-by":"publisher","first-page":"18669","DOI":"10.1038\/srep18669","article-title":"Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers","volume":"6","author":"Nath","year":"2016","journal-title":"Sci. Rep."},{"key":"2025060909204987000_bib37","doi-asserted-by":"publisher","first-page":"5069","DOI":"10.1038\/s41467-018-07339-y","article-title":"Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels","volume":"9","author":"Novo","year":"2018","journal-title":"Nat. Commun."},{"key":"2025060909204987000_bib38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/bs.mie.2016.09.076","article-title":"Application of CRISPR\/Cas9 to autophagy research","volume":"588","author":"O\u2019Prey","year":"2017","journal-title":"Methods Enzymol."},{"key":"2025060909204987000_bib39","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/ncb2000","article-title":"Rab27a and Rab27b control different steps of the exosome secretion pathway","volume":"12","author":"Ostrowski","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"2025060909204987000_bib40","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s42255-019-0159-z","article-title":"The creatine-phosphagen system is mechanoresponsive in pancreatic adenocarcinoma and fuels invasion and metastasis","volume":"2","author":"Papalazarou","year":"2020","journal-title":"Nat. Metab."},{"key":"2025060909204987000_bib41","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nature20791","article-title":"Targeting metastasis-initiating cells through the fatty acid receptor CD36","volume":"541","author":"Pascual","year":"2017","journal-title":"Nature"},{"key":"2025060909204987000_bib42","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nrc.2017.6","article-title":"Pre-metastatic niches: Organ-specific homes for metastases","volume":"17","author":"Peinado","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"2025060909204987000_bib43","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1038\/s41467-020-15960-z","article-title":"LipidCreator workbench to probe the lipidomic landscape","volume":"11","author":"Peng","year":"2020","journal-title":"Nat. Commun."},{"key":"2025060909204987000_bib44","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh2023","article-title":"Loss of attachment promotes proline accumulation and excretion in cancer cells","volume":"9","author":"Pilley","year":"2023","journal-title":"Sci. Adv."},{"key":"2025060909204987000_bib45","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nature15726","article-title":"Oxidative stress inhibits distant metastasis by human melanoma cells","volume":"527","author":"Piskounova","year":"2015","journal-title":"Nature"},{"key":"2025060909204987000_bib46","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202006049","article-title":"PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness","volume":"220","author":"Rabas","year":"2021","journal-title":"J. Cell Biol."},{"key":"2025060909204987000_bib47","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.molcel.2020.11.027","article-title":"In vivo evidence for serine biosynthesis-defined sensitivity of lung metastasis, but not of primary breast tumors, to mTORC1 inhibition","volume":"81","author":"Rinaldi","year":"2021","journal-title":"Mol. Cell"},{"key":"2025060909204987000_bib48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2205456119","article-title":"Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures","volume":"119","author":"Roshanzamir","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025060909204987000_bib49","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"2025060909204987000_bib50","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019103334","article-title":"Proline biosynthesis is a vent for TGF\u03b2-induced mitochondrial redox stress","volume":"39","author":"Schw\u00f6rer","year":"2020","journal-title":"EMBO J."},{"key":"2025060909204987000_bib51","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1247005","article-title":"Genome-scale CRISPR-Cas9 knockout screening in human cells","volume":"343","author":"Shalem","year":"2014","journal-title":"Science"},{"key":"2025060909204987000_bib52","doi-asserted-by":"publisher","first-page":"292","DOI":"10.3390\/metabo10070292","article-title":"Optimized protocol for the in situ derivatization of glutathione with N-ethylmaleimide in cultured cells and the simultaneous determination of glutathione\/glutathione disulfide ratio by HPLC-UV-QTOF-MS","volume":"10","author":"Sun","year":"2020","journal-title":"Metabolites"},{"key":"2025060909204987000_bib53","doi-asserted-by":"publisher","first-page":"425","DOI":"10.3390\/cancers13030425","article-title":"Cysteine and folate metabolism are targetable vulnerabilities of metastatic colorectal cancer","volume":"13","author":"Tarrag\u00f3-Celada","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2025060909204987000_bib54","doi-asserted-by":"publisher","DOI":"10.3791\/3089","article-title":"Organotypic collagen I assay: A malleable platform to assess cell behaviour in a 3-dimensional context","author":"Timpson","year":"2011","journal-title":"J. Vis. Exp."},{"key":"2025060909204987000_bib55","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.1038\/s41467-018-05077-9","article-title":"Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts","volume":"9","author":"Torralba","year":"2018","journal-title":"Nat. Commun."},{"key":"2025060909204987000_bib56","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1126\/science.1153124","article-title":"Ceramide triggers budding of exosome vesicles into multivesicular endosomes","volume":"319","author":"Trajkovic","year":"2008","journal-title":"Science"},{"key":"2025060909204987000_bib57","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"2025060909204987000_bib58","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau7314","article-title":"Improving the metabolic fidelity of cancer models with a physiological cell culture medium","volume":"5","author":"Vande Voorde","year":"2019","journal-title":"Sci. Adv."},{"key":"2025060909204987000_bib59","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/s41589-022-01154-9","article-title":"Hepatic glutamine synthetase controls N5-methylglutamine in homeostasis and cancer","volume":"19","author":"Villar","year":"2023","journal-title":"Nat. Chem. Biol."},{"key":"2025060909204987000_bib60","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41586-023-06114-4","article-title":"Tumour extracellular vesicles and particles induce liver metabolic dysfunction","volume":"618","author":"Wang","year":"2023","journal-title":"Nature"},{"key":"2025060909204987000_bib61","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41586-021-04025-w","article-title":"SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells","volume":"599","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"2025060909204987000_bib62","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000880","article-title":"A FIJI macro for quantifying pattern in extracellular matrix","volume":"4","author":"Wershof","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"2025060909204987000_bib63","doi-asserted-by":"publisher","first-page":"110320","DOI":"10.1016\/j.celrep.2022.110320","article-title":"Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions","volume":"38","author":"Westbrook","year":"2022","journal-title":"Cell Rep."},{"key":"2025060909204987000_bib64","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.1038\/s41467-023-39401-9","article-title":"SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells","volume":"14","author":"Yan","year":"2023","journal-title":"Nat. Commun."}],"container-title":["Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/doi\/10.1083\/jcb.202405061\/1945947\/jcb_202405061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/doi\/10.1083\/jcb.202405061\/1945947\/jcb_202405061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:20:59Z","timestamp":1749460859000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/224\/8\/e202405061\/278040\/Metabolic-adaptations-of-micrometastases-alter-EV"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":64,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,4]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.202405061","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.05.12.593552","asserted-by":"object"}]},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"article-number":"e202405061"}}