{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:56:55Z","timestamp":1781917015879,"version":"3.54.5"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":61,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM135391"],"award-info":[{"award-number":["GM135391"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50 CA180995"],"award-info":[{"award-number":["P50 CA180995"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Castration-resistant prostate cancer (CRPC) progresses despite androgen deprivation therapy, as cancer cells adapt to grow without testosterone, becoming more aggressive and prone to metastasis. CRPC biology complicates the development of effective therapies, posing challenges for patient care. Recent gene-expression and metabolomics studies highlight the Hexosamine Biosynthetic Pathway (HBP) as a critical player, with key components like GNPNAT1 (Glucosamine-phosphate N-acetyltransferase 1) being downregulated in CRPC. GNPNAT1 knockdown in pre-clinical models has been shown to increase growth and metastasis in CRPC tumors, though the mechanisms remain unclear.<\/jats:p>\n                  <jats:p>To investigate the cellular basis of these CRPC phenotypes, we generated a CRISPR-Cas9 knockout model of GNPNAT1 in 22Rv1 CRPC cells, analyzing its impact on transcriptomic and glycoproteomic profiles of cells. We find that HBP inhibition disrupts the cytoskeleton, altering mitotic progression and promoting uncontrolled growth. GNPNAT1 KO cells showed reduced levels of cytoskeletal filaments, such as actin and microtubules, leading to cell structure disorganization and chromosomal mis-segregation. GNPNAT1 inhibition also activated PI3K\/AKT signaling, promoting cell proliferation, impaired cell adhesion by mis-localizing Eph Receptor B6, enhancing migration via the RhoA (Ras homolog family member A) pathway and promoting epithelial-to-mesenchymal transition. These findings suggest that HBP plays a critical role in regulating CRPC cell behavior, and targeting this pathway could provide a novel therapeutic approach.<\/jats:p>","DOI":"10.1186\/s12964-026-02756-9","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T03:04:06Z","timestamp":1774667046000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The hexosamine biosynthetic pathway alters the cytoskeleton to modulate cell proliferation and migration in aggressive prostate cancer"],"prefix":"10.1186","volume":"24","author":[{"given":"Rajina","family":"Shakya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Suraneni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Rahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3990-5724","authenticated-orcid":false,"given":"Michael Y.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Cousino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine B.","family":"Magdongon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Gajjela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil B.","family":"Mattamana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Zaslavsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh S","family":"Palapattu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Sreekumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dileep","family":"Varma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"2756_CR1","doi-asserted-by":"crossref","unstructured":"Rawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019;10(2):63\u201389. Available from: http:\/\/www.wjon.org\/index.php\/WJON\/article\/view\/1191.","DOI":"10.14740\/wjon1191"},{"key":"2756_CR2","doi-asserted-by":"publisher","unstructured":"Harris WP, Mostaghel EA, Nelson PS, Montgomery B. Androgen deprivation therapy: Progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol. 2009;6(2):76\u201385.\u00a0https:\/\/doi.org\/10.1038\/ncpuro1296.","DOI":"10.1038\/ncpuro1296"},{"issue":"3","key":"2756_CR3","first-page":"365","volume":"4","author":"T Chandrasekar","year":"2015","unstructured":"Chandrasekar T, Yang JC, Gao AC, Evans CP. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4(3):365\u201380.","journal-title":"Transl Androl Urol"},{"key":"2756_CR4","doi-asserted-by":"publisher","unstructured":"Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer. 2015;15(12):701\u201311.\u00a0https:\/\/doi.org\/10.1038\/nrc4016","DOI":"10.1038\/nrc4016"},{"key":"2756_CR5","doi-asserted-by":"publisher","unstructured":"DeWane G, Salvi AM, DeMali KA. Fueling the cytoskeleton-links between cell metabolism and actin remodeling. J Cell Sci. 2021;134(3):jcs248385. https:\/\/doi.org\/10.1242\/jcs.248385.","DOI":"10.1242\/jcs.248385"},{"key":"2756_CR6","doi-asserted-by":"publisher","unstructured":"Liu G, Li J, Wu C. Reciprocal regulation of actin filaments and cellular metabolism. Eur J Cell Biol. 2022;101(4):151281. https:\/\/doi.org\/10.1016\/j.ejcb.2022.151281.","DOI":"10.1016\/j.ejcb.2022.151281"},{"issue":"4","key":"2756_CR7","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1080\/21541248.2020.1826781","volume":"12","author":"M De Piano","year":"2021","unstructured":"De Piano M, Manuelli V, Zadra G, Loda M, Muir G, Chandra A, et al. Exploring a role for fatty acid synthase in prostate cancer cell migration. Small GTPases. 2021;12(4):265\u201372.","journal-title":"Small GTPases"},{"key":"2756_CR8","doi-asserted-by":"publisher","unstructured":"Kaushik AK, Shojaie A, Panzitt K, Sonavane R, Venghatakrishnan H, Manikkam M, et al. Inhibition of the hexosamine biosynthetic pathway promotes castration-resistant prostate cancer. Nat Commun. 2016;7:11612. https:\/\/doi.org\/10.1038\/ncomms11612.","DOI":"10.1038\/ncomms11612."},{"key":"2756_CR9","doi-asserted-by":"publisher","unstructured":"Parker AL, Kavallaris M, McCarroll JA. Microtubules and their role in cellular stress in cancer. Front Oncol. 2014;4:153. https:\/\/doi.org\/10.3389\/fonc.2014.00153.","DOI":"10.3389\/fonc.2014.00153"},{"key":"2756_CR10","doi-asserted-by":"publisher","unstructured":"Akella NM, Ciraku L, Reginato MJ. Fueling the fire: Emerging role of the hexosamine biosynthetic pathway in cancer. BMC Biol. 2019;17(1):52. https:\/\/doi.org\/10.1186\/s12915-019-0671-3.","DOI":"10.1186\/s12915-019-0671-3"},{"key":"2756_CR11","doi-asserted-by":"publisher","unstructured":"Paneque A, Fortus H, Zheng J, Werlen G, Jacinto E. The Hexosamine Biosynthesis Pathway: Regulation and Function. Genes (Basel). 2023;14(4):933. https:\/\/doi.org\/10.3390\/genes14040933.","DOI":"10.3390\/genes14040933"},{"key":"2756_CR12","doi-asserted-by":"publisher","unstructured":"Muniz de Queiroz R, Oliveira IA, Piva B, Cat\u00e3o FB, Rodrigues B da C, Pascoal A da C, et al. Hexosamine Biosynthetic Pathway and Glycosylation Regulate Cell Migration in Melanoma Cells. Front Oncol. 2019;9:116. https:\/\/doi.org\/10.3389\/fonc.2019.00116.","DOI":"10.3389\/fonc.2019.00116"},{"key":"2756_CR13","doi-asserted-by":"publisher","unstructured":"Brooks Robey R, Weisz J, Kuemmerle N, Salzberg AC, Berg A, Brown DG, et al. Metabolic reprogramming and dysregulated metabolism: Cause, consequence and\/or enabler of environmental carcinogenesis? Carcinogenesis. 2015;36:S203\u201331. https:\/\/doi.org\/10.1093\/carcin\/bgv037.","DOI":"10.1093\/carcin\/bgv037"},{"key":"2756_CR14","doi-asserted-by":"publisher","unstructured":"Liu W, Jiang K, Wang J, Mei T, Zhao M, Huang D. Upregulation of GNPNAT1 Predicts Poor Prognosis and Correlates With Immune Infiltration in Lung Adenocarcinoma. Front Mol Biosci. 2021;8:605754. https:\/\/doi.org\/10.3389\/fmolb.2021.605754.","DOI":"10.3389\/fmolb.2021.605754"},{"key":"2756_CR15","doi-asserted-by":"publisher","unstructured":"Hanover G, Vizeacoumar FS, Banerjee SL, Nair R, Dahiya R, Osornio-Hernandez AI, et al. Integration of cancer-related genetic landscape of Eph receptors and ephrins with proteomics identifies a crosstalk between EPHB6 and EGFR. Cell Rep. 2023;42(7):1\u201324. https:\/\/doi.org\/10.1016\/j.celrep.2023.112670.","DOI":"10.1016\/j.celrep.2023.112670"},{"key":"2756_CR16","doi-asserted-by":"publisher","unstructured":"Pergaris A, Danas E, Goutas D, Sykaras AG, Soranidis A, Theocharis S. The clinical impact of the eph\/ephrin system in cancer: Unwinding the thread. Int J Mol Sci. 2021;22(16):8412. https:\/\/doi.org\/10.3390\/ijms22168412.","DOI":"10.3390\/ijms22168412"},{"key":"2756_CR17","doi-asserted-by":"publisher","unstructured":"Darling TK, Lamb TJ. Emerging roles for Eph receptors and ephrin ligands in immunity. Front Immunol. 2019;10:1473. https:\/\/doi.org\/10.3389\/fimmu.2019.01473.","DOI":"10.3389\/fimmu.2019.01473"},{"key":"2756_CR18","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/nrc2806","volume":"10","author":"EB Pasquale","year":"2010","unstructured":"Pasquale EB. Eph receptors and ephrins in cancer: Bidirectional signalling and beyond. Nat Rev Cancer. 2010;10:165\u201380.","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"2756_CR19","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1158\/0008-5472.CAN-09-1710","volume":"70","author":"L Truitt","year":"2010","unstructured":"Truitt L, Freywald T, DeCoteau J, Sharfe N, Freywald A. The EphB6 receptor cooperates with c-Cbl to regulate the behavior of breast cancer cells. Cancer Res. 2010;70(3):1141\u201353.","journal-title":"Cancer Res"},{"key":"2756_CR20","doi-asserted-by":"publisher","unstructured":"Guo X, Yang Y, Tang J, Xiang J. Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity. Cell Communication and Signaling . 2024;22(1):299. https:\/\/doi.org\/10.1186\/s12964-024-01580-3.","DOI":"10.1186\/s12964-024-01580-3"},{"key":"2756_CR21","doi-asserted-by":"publisher","unstructured":"Miao H, Wang B. EphA receptor signaling-Complexity and emerging themes. Semin Cell Dev Biol. 2012;23(1):16\u201325. https:\/\/doi.org\/10.1016\/j.semcdb.2011.10.013.","DOI":"10.1016\/j.semcdb.2011.10.013"},{"key":"2756_CR22","doi-asserted-by":"publisher","unstructured":"Buckens OJ, El Hassouni B, Giovannetti E, Peters GJ. The role of Eph receptors in cancer and how to target them: novel approaches in cancer treatment. Expert Opin Investig Drugs. 2020;29(6):567\u201382. https:\/\/doi.org\/10.1080\/13543784.2020.1762566.","DOI":"10.1080\/13543784.2020.1762566"},{"key":"2756_CR23","doi-asserted-by":"publisher","unstructured":"Wang Q, Yang X, Xu Y, Shen Z, Cheng H, Cheng F, et al. RhoA\/Rho-kinase triggers epithelial-mesenchymal transition in mesothelial cells and contributes to the pathogenesis of dialysis-related peritoneal fibrosis. Oncotarget. 2018;9(18):14397\u2013412. Available from: https:\/\/doi.org\/10.18632\/oncotarget.24208.","DOI":"10.18632\/oncotarget.24208"},{"key":"2756_CR24","doi-asserted-by":"publisher","unstructured":"Nishizuka M, Komada R, Imagawa M. Knockdown of RhoE Expression Enhances TGF-\u03b2-Induced EMT (epithelial-to-mesenchymal transition) in Cervical Cancer HeLa Cells. Int J Mol Sci. 2019;20(19):4697. https:\/\/doi.org\/10.3390\/ijms20194697.","DOI":"10.3390\/ijms20194697"},{"key":"2756_CR25","doi-asserted-by":"publisher","unstructured":"Liu B, Dong H, Lin X, Yang X, Yue X, Yang J, et al. RND3 promotes Snail 1 protein degradation and inhibits glioblastoma cell migration and invasion. Oncotarget. 2016;7(50):82411\u201323. Available from: https:\/\/doi.org\/10.18632\/oncotarget.12396.","DOI":"10.18632\/oncotarget.12396"},{"key":"2756_CR26","doi-asserted-by":"publisher","unstructured":"Bhowmick NA, Ghiassi M, Bakin A, Aakre M, Lundquist CA, Engel ME, et al. Transforming Growth Factor-1 Mediates Epithelial to Mesenchymal Transdifferentiation through a RhoA-dependent Mechanism. Mol Biol Cell. 2001;12:27\u201336. https:\/\/doi.org\/10.1091\/mbc.12.1.27.","DOI":"10.1091\/mbc.12.1.27"},{"key":"2756_CR27","doi-asserted-by":"publisher","unstructured":"Jinka R, Kapoor R, Sistla PG, Raj TA, Pande G. Alterations in cell-extracellular matrix interactions during progression of cancers. Int J Cell Biol. 2012;2012(1):219196. https:\/\/doi.org\/10.1155\/2012\/219196.","DOI":"10.1155\/2012\/219196"},{"issue":"24","key":"2756_CR28","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1101\/gad.1985910","volume":"24","author":"KE Wellen","year":"2010","unstructured":"Wellen KE, Lu C, Mancuso A, Lemons JMS, Ryczko M, Dennis JW, et al. The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev. 2010;24(24):2784\u201399.","journal-title":"Genes Dev"},{"key":"2756_CR29","doi-asserted-by":"publisher","unstructured":"DeLiberty JM, Robb R, Gates CE, Bryant KL. Unraveling and targeting RAS-driven metabolic signaling for therapeutic gain. Adv Cancer Res. 2022;153:267\u2013304.https:\/\/doi.org\/10.1016\/bs.acr.2021.07.010.","DOI":"10.1016\/bs.acr.2021.07.010"},{"key":"2756_CR30","doi-asserted-by":"publisher","unstructured":"G\u00f3mez-Cebri\u00e1n N, Poveda JL, Pineda-Lucena A, Puchades-Carrasco L. Metabolic Phenotyping in Prostate Cancer Using Multi-Omics Approaches. Cancers (Basel). 2022;14(3):596. https:\/\/doi.org\/10.3390\/cancers14030596.","DOI":"10.3390\/cancers14030596"},{"key":"2756_CR31","doi-asserted-by":"publisher","unstructured":"Le Minh G, Esquea EM, Young RG, Huang J, Reginato MJ. On a sugar high: Role of O-GlcNAcylation in cancer. Journal of Biological Chemistry. 2023;299(11):105344. https:\/\/doi.org\/10.1016\/j.jbc.2023.105344.","DOI":"10.1016\/j.jbc.2023.105344"},{"issue":"1","key":"2756_CR32","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1074\/mcp.M115.052381","volume":"15","author":"S Ren","year":"2016","unstructured":"Ren S, Shao Y, Zhao X, Hong CS, Wang F, Lu X, et al. Integration of metabolomics and transcriptomics reveals major metabolic pathways and potential biomarker involved in prostate cancer. Mol Cell Proteomics. 2016;15(1):154\u201363.","journal-title":"Mol Cell Proteomics"},{"key":"2756_CR33","doi-asserted-by":"publisher","unstructured":"Godek KM, Compton DA. Quantitative methods to measure aneuploidy and chromosomal instability. Methods Cell Biol. 2018;144:15\u201332. https:\/\/doi.org\/10.1016\/bs.mcb.2018.03.002.","DOI":"10.1016\/bs.mcb.2018.03.002"},{"key":"2756_CR34","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/embor.2012.55","volume":"13","author":"AJ Holland","year":"2012","unstructured":"Holland AJ, Cleveland DW. Losing balance: The origin and impact of aneuploidy in cancer. EMBO Rep. 2012;13:501\u201314.","journal-title":"EMBO Rep"},{"issue":"2","key":"2756_CR35","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.cels.2019.06.007","volume":"9","author":"Y Chen","year":"2019","unstructured":"Chen Y, Chen S, Li K, Zhang Y, Huang X, Li T, et al. Overdosage of Balanced Protein Complexes Reduces Proliferation Rate in Aneuploid Cells. Cell Syst. 2019;9(2):129\u2013e1425.","journal-title":"Cell Syst"},{"key":"2756_CR36","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.tig.2011.07.003","volume":"27","author":"JM Sheltzer","year":"2011","unstructured":"Sheltzer JM, Amon A. The aneuploidy paradox: Costs and benefits of an incorrect karyotype. Trends Genet. 2011;27:446\u201353.","journal-title":"Trends Genet"},{"key":"2756_CR37","doi-asserted-by":"publisher","unstructured":"Akhshi TK, Wernike D, Piekny A. Microtubules and actin crosstalk in cell migration and division. Cytoskeleton. 2014;71(1):1\u201323. https:\/\/doi.org\/10.1002\/cm.21150.","DOI":"10.1002\/cm.21150"},{"key":"2756_CR38","doi-asserted-by":"publisher","unstructured":"Coles CH, Bradke F. Coordinating Neuronal Actin-Microtubule Dynamics. Current Biology. 2015;25(15):R677\u201391. https:\/\/doi.org\/10.1016\/j.cub.2015.06.020.","DOI":"10.1016\/j.cub.2015.06.020"},{"key":"2756_CR39","doi-asserted-by":"publisher","unstructured":"Tang DD, Gerlach BD. The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration. Respir Res. 2017;18(1):54. https:\/\/doi.org\/10.1186\/s12931-017-0544-7.","DOI":"10.1186\/s12931-017-0544-7"},{"key":"2756_CR40","doi-asserted-by":"publisher","unstructured":"Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO\u00a0and regulation of apoptosis. Biochim Biophys Acta Mol Cell Res. 2011;1813(11):1978\u201386. https:\/\/doi.org\/10.1016\/j.bbamcr.2011.03.010. PubMed PMID: 21440011.","DOI":"10.1016\/j.bbamcr.2011.03.010"},{"key":"2756_CR41","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1172\/JCI39104","volume":"119","author":"R Kalluri","year":"2009","unstructured":"Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119:1420\u20138.","journal-title":"J Clin Invest"},{"key":"2756_CR42","doi-asserted-by":"publisher","unstructured":"Chen T, You Y, Jiang H, Wang ZZ. Epithelial\u2013mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol. 2017;232(12):3261\u201372. https:\/\/doi.org\/10.1002\/jcp.25797.","DOI":"10.1002\/jcp.25797"},{"key":"2756_CR43","doi-asserted-by":"publisher","unstructured":"Liang P, Wu Y, Zheng S, Zhang J, Yang S, Wang J, et al. Paxillin phase separation promotes focal adhesion assembly and integrin signaling. Journal of Cell Biology. 2024;223(4):e202209027. https:\/\/doi.org\/10.1083\/jcb.202209027.","DOI":"10.1083\/jcb.202209027"},{"key":"2756_CR44","doi-asserted-by":"crossref","unstructured":"Wolosowicz M, Prokopiuk S, Kaminski TW. Matrix Metalloproteinase-9 (MMP-9) as a Therapeutic Target: Insights into Molecular Pathways and Clinical Applications. Pharmaceutics. 2025 Nov 1;17(11):1425.","DOI":"10.3390\/pharmaceutics17111425"},{"key":"2756_CR45","doi-asserted-by":"crossref","unstructured":"Zhao YW, Ma W, Jiang F, Xie Y, Tang L. Upregulation of matrix metalloproteinase 14(MMP14) is associated with poor prognosis in renal clear cell carcinoma-abioinformatics analysis. Transl Androl Urol. 2022;11(11):1523\u201334.","DOI":"10.21037\/tau-22-619"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-026-02756-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02756-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02756-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:01:49Z","timestamp":1781643709000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-026-02756-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2756"],"URL":"https:\/\/doi.org\/10.1186\/s12964-026-02756-9","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,28]]},"assertion":[{"value":"27 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"311"}}