@article{61fe8e4c76264bdcbfaf7d263b62f744,
title = "Loss of attachment promotes proline accumulation and excretion in cancer cells",
abstract = "Previous studies have revealed a role for proline metabolism in supporting cancer development and metastasis. In this study, we show that many cancer cells respond to loss of attachment by accumulating and secreting proline. Detached cells display reduced proliferation accompanied by a general decrease in overall protein production and de novo amino acid synthesis compared to attached cells. However, proline synthesis was maintained under detached conditions. Furthermore, while overall proline incorporation into proteins was lower in detached cells compared to other amino acids, there was an increased production of the proline-rich protein collagen. The increased excretion of proline from detached cells was also shown to be used by macrophages, an abundant and important component of the tumor microenvironment. Our study suggests that detachment induced accumulation and secretion of proline may contribute to tumor progression by supporting increased production of extracellular matrix and providing proline to surrounding stromal cells.",
author = "Pilley, {Steven E.} and Marc Hennequart and Anke Vandekeere and Julianna Blagih and Legrave, {Nathalie M.} and Fendt, {Sarah Maria} and Vousden, {Karen H.} and Labuschagne, {Christiaan F.}",
note = "Funding Information: This work was supported by Cancer Research UK grant C596/A26855 (K.H.V.); Francis Crick Institute, which receives its core funding from Francis Crick Institute/Cancer Research UK CC2073 (K.H.V.), Francis Crick Institute/UK Medical Research Council CC2073 (K.H.V.), and Francis Crick Institute/Wellcome Trust CC2073 (K.H.V.); the Kuok Family Fellowship (J.B.); ERC Consolidator Grant Agreement no. 771486 (S.-M.F.); MetaRegulation (S.-M.F.); FWO Projects (S.M.F.); Beug Foundation (S.-M.F.); Fonds Baillet Latour KU Leuven (S.-M.F.); Stichting tegen Kanker (S.-M.F.); and FWO PhD fellowship (A.V.) Funding Information: Acknowledgments Funding:ThisworkwassupportedbyCancerResearchUKgrantC596/A26855(K.H.V .); Francis Crick Institute, which receivesits core funding fromFrancis Crick Institute/Cancer Research UK CC2073(K.H.V .), FrancisCrickInstitute/UKMedicalResearchCouncilCC2073(K.H.V .), andFrancis CrickInstitute/W ellcome TrustCC2073(K.H.V .); theKuokFamilyFellowship(J.B.);ERC ConsolidatorGrantAgreementno.771486(S.-M.F .); MetaRegulation(S.-M.F .); FWOProjects(S.-M.F .); BeugFoundation,(S.-M.F .); FondsBailletLatour,KULeuven(S.-M.F .); Stichtingtegen Kanker(S.-M.F .); andFWOPhDfellowship(A.V .). Authorcontributions:Conceptualizationand design:S.E.P ., M.H.,K.H.V ., andC.F .L. Investigation:S.E.P ., A.V ., M.H.,andJ.B.Advice:S.-M.F .LC-MS experiments:N.M.L.Writing—originaldraft:S.E.P ., M.H.,K.H.V ., andC.F .L. Writing—reviewand editing:Allauthors.Competinginterests:K.H.V .isontheboardofdirectorsandshareholderof BristolMyersSquibbandonthescienceadvisoryboard(withstockoptions)ofPMVPharma, RAZETherapeutics,VolastraPharmaceuticals,andKovinaTherapeutics.K.H.V .isontheSABof LudwigCancerandacofounderandconsultantofFaethTherapeutics.K.H.V .hasbeenin receipt of research funding from Astex Pharmaceuticals and AstraZeneca and contributed to CRUKCancerResearchT echnology filingofpatentapplicationWO/2017/144877.S.-M.F .has received funding fromBayer AG Merck Black Belt Therapeutics Gilead and Alesta Therapeutics hasconsultedforFund+andisintheadvisoryboardofAlestaTherapeutics.Theotherauthors declarethattheyhavenocompetinginterests.Dataandmaterialsavailability:P5CS-K Ocells areavailableonrequestfromkaren.vousden@crick.ac.uk.Alldataneededtoevaluatethe conclusionsinthepaperarepresentinthepaperand/ortheSupplementaryMaterials. Publisher Copyright: {\textcopyright} 2023 The Authors.",
year = "2023",
month = sep,
day = "8",
doi = "10.1126/sciadv.adh2023",
language = "English",
volume = "9",
pages = "eadh2023",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "36",
}
