{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:05:51Z","timestamp":1777489551220,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["PD\/BDE\/150707\/2020"],"award-info":[{"award-number":["PD\/BDE\/150707\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["2021.06297.BD"],"award-info":[{"award-number":["2021.06297.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Brain metastasis (BrM) is a devastating end-stage neurological complication that occurs in up to 50% of human epidermal growth factor receptor 2-positive (HER2+)\u2005breast cancer (BC) patients. Understanding how disseminating tumor cells manage to cross the blood\u2013brain barrier (BBB) is essential for developing effective preventive strategies. We identified the ecto-nucleotidase ENPP1 (ectonucleotide pyrophosphatase\/phosphodiesterase 1) as specifically enriched in the secretome of HER2+ brain metastatic cells, prompting us to explore its impact on BBB dysfunction and BrM formation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used in vitro BBB and in vivo premetastatic mouse models to evaluate the effect of tumor-secreted ENPP1 on brain vascular permeability. BBB integrity was analyzed by real-time fluorescence imaging of 20 kDa Cy7.5-dextran extravasation and immunofluorescence staining of adherens and tight junction proteins. Pro-metastatic effects of ENPP1 were evaluated in an experimental brain metastatic model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Systemically secreted ENPP1 from primary breast tumors impaired the integrity of BBB with loss of tight and adherens junction proteins early before the onset of BrM. Mechanistically, ENPP1 induced endothelial cell dysfunction by impairing insulin signaling and its downstream AKT\/GSK3\u03b2\/\u03b2-catenin pathway. Genetic ablation of ENPP1 from HER2+ brain metastatic cells prevented endothelial cell dysfunction and reduced metastatic burden while prolonging the overall and metastasis-free survival of mice. Furthermore, plasmatic ENPP1 levels correlate with brain metastatic burden and inversely with overall survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We demonstrated that metastatic BC cells exploit the ENPP1 signaling for cell transmigration across the BBB and brain colonization. Our data implicate ENPP1 as a potential biomarker for poor prognosis and early detection of BrM in HER2+ BC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae169","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T11:25:46Z","timestamp":1724844346000},"page":"167-183","source":"Crossref","is-referenced-by-count":15,"title":["ENPP1 induces blood\u2013brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-9572","authenticated-orcid":false,"given":"Liliana","family":"Santos","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS) and Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7378-0752","authenticated-orcid":false,"given":"Francesca","family":"Tomatis","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Institute of Interdisciplinary Research, University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1658-9326","authenticated-orcid":false,"given":"Hugo R S","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Clinical Academic Center of Coimbra (CACC) , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-2220","authenticated-orcid":false,"given":"Sara F F","family":"Almeida","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS) and Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"given":"Edward","family":"Ciputra","sequence":"additional","affiliation":[{"name":"Clinical Academic Center of Coimbra (CACC) , Coimbra ,","place":["Portugal"]},{"name":"Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-6653","authenticated-orcid":false,"given":"Jos\u00e9","family":"Sereno","sequence":"additional","affiliation":[{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS) and Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7844-0167","authenticated-orcid":false,"given":"Rui","family":"Almeida","sequence":"additional","affiliation":[{"name":"Pathology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6812-7305","authenticated-orcid":false,"given":"Paulo","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Pathology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9233","authenticated-orcid":false,"given":"Ana Sofia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Cancer Metastasis Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S) , Porto ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3449-0522","authenticated-orcid":false,"given":"Jo\u00e3o N","family":"Moreira","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7802-8690","authenticated-orcid":false,"given":"Ana P","family":"Silva","sequence":"additional","affiliation":[{"name":"Clinical Academic Center of Coimbra (CACC) , Coimbra ,","place":["Portugal"]},{"name":"Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-9302","authenticated-orcid":false,"given":"Lino","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Institute of Interdisciplinary Research, University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4145-854X","authenticated-orcid":false,"given":"Antero J","family":"Abrunhosa","sequence":"additional","affiliation":[{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS) and Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra , Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-4129","authenticated-orcid":false,"given":"C\u00e9lia M","family":"Gomes","sequence":"additional","affiliation":[{"name":"Clinical Academic Center of Coimbra (CACC) , Coimbra ,","place":["Portugal"]},{"name":"Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra , Coimbra ,","place":["Portugal"]},{"name":"Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra , Coimbra ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"issue":"1","key":"2025011312202754100_CIT0001","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s11912-011-0203-y","article-title":"Epidemiology of brain metastases","volume":"14","author":"Nayak","year":"2012","journal-title":"Curr Oncol Rep."},{"issue":"7","key":"2025011312202754100_CIT0002","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/annonc\/mdq625","article-title":"Cerebral metastases in metastatic breast cancer: Disease-specific risk factors and survival","volume":"22","author":"Heitz","year":"2011","journal-title":"Ann Oncol."},{"issue":"1","key":"2025011312202754100_CIT0003","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1186\/s12885-021-08708-5","article-title":"Prognostic factors of brain metastasis and survival among HER2-positive metastatic breast cancer patients: A systematic literature review","volume":"21","author":"Hackshaw","year":"2021","journal-title":"BMC Cancer"},{"issue":"1","key":"2025011312202754100_CIT0004","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41416-020-01161-4","article-title":"The lingering mysteries of metastatic recurrence in breast cancer","volume":"124","author":"Riggio","year":"2021","journal-title":"Br J Cancer."},{"key":"2025011312202754100_CIT0005","first-page":"294","article-title":"Impact of breast cancer cells secretome on the brain metastatic niche remodeling","volume-title":"Semin Cell Dev Biol","author":"Carvalho","year":"2020"},{"issue":"3","key":"2025011312202754100_CIT0006","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s43018-023-00519-w","article-title":"Reciprocal interactions between innate immune cells and astrocytes facilitate neuroinflammation and brain metastasis via lipocalin-2","volume":"4","author":"Adler","year":"2023","journal-title":"Nature Cancer"},{"issue":"1","key":"2025011312202754100_CIT0007","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41568-019-0205-x","article-title":"The blood\u2013brain barrier and blood\u2013tumour barrier in brain tumours and metastases","volume":"20","author":"Arvanitis","year":"2020","journal-title":"Nat Rev Cancer."},{"issue":"10","key":"2025011312202754100_CIT0008","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.tins.2015.08.003","article-title":"The molecular constituents of the blood\u2013brain barrier","volume":"38","author":"Chow","year":"2015","journal-title":"Trends Neurosci."},{"issue":"1","key":"2025011312202754100_CIT0009","doi-asserted-by":"crossref","first-page":"6716","DOI":"10.1038\/ncomms7716","article-title":"Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood\u2013brain barrier","volume":"6","author":"Tominaga","year":"2015","journal-title":"Nat Commun."},{"issue":"1","key":"2025011312202754100_CIT0010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/7461727","article-title":"Exosomes derived from brain metastatic breast cancer cells destroy the blood-brain barrier by carrying lncRNA GS1-600G8. 5","volume":"2020","author":"Lu","year":"2020","journal-title":"Biomed Res Int."},{"issue":"52","key":"2025011312202754100_CIT0011","doi-asserted-by":"crossref","first-page":"e2313693120","DOI":"10.1073\/pnas.2313693120","article-title":"ENPP1 is an innate immune checkpoint of the anticancer cGAMP\u2013STING pathway in breast cancer","volume":"120","author":"Wang","year":"2023","journal-title":"Proc Natl Acad Sci USA."},{"key":"2025011312202754100_CIT0012","doi-asserted-by":"crossref","DOI":"10.21203\/rs.3.rs-779340\/v1","volume-title":"ENPP1 Is Correlated With Insulin Resistance and Lipid Molecules in PCOS Rats","author":"Xia","year":"2021"},{"key":"2025011312202754100_CIT0013","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fendo.2018.00098","article-title":"Uric acid impairs insulin signaling by promoting Enpp1 binding to insulin receptor in human umbilical vein endothelial cells","volume":"9","author":"Tassone","year":"2018","journal-title":"Front Endocrinol."},{"issue":"1","key":"2025011312202754100_CIT0014","first-page":"10.4172\/2325-9736.1000e103","article-title":"New insights into the role of ENPP1 in insulin resistance","volume":"1","author":"Pan","year":"2012","journal-title":"J Metabonomics Metab"},{"issue":"1","key":"2025011312202754100_CIT0015","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1210\/er.2007-0004","article-title":"The role of membrane glycoprotein plasma cell antigen 1\/ectonucleotide pyrophosphatase phosphodiesterase 1 in the pathogenesis of insulin resistance and related abnormalities","volume":"29","author":"Goldfine","year":"2008","journal-title":"Endocr Rev."},{"issue":"12","key":"2025011312202754100_CIT0016","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/ncpendmet0367","article-title":"Mechanisms of disease: Ectonucleotide pyrophosphatase phosphodiesterase 1 as a\u2019gatekeeper\u2019of insulin receptors","volume":"2","author":"Abate","year":"2006","journal-title":"Nat Clin Pract Endocrinol Metab"},{"issue":"1","key":"2025011312202754100_CIT0017","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41540-022-00235-8","article-title":"Mapping the dynamics of insulin-responsive pathways in the blood\u2013brain barrier endothelium using time-series transcriptomics data","volume":"8","author":"Wang","year":"2022","journal-title":"NPJ Syst Biol Appl."},{"issue":"1","key":"2025011312202754100_CIT0018","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/ncpendmet0366","article-title":"Mechanisms of disease: Endothelial dysfunction in insulin resistance and diabetes","volume":"3","author":"Rask-Madsen","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab."},{"issue":"1","key":"2025011312202754100_CIT0019","doi-asserted-by":"crossref","first-page":"e16114","DOI":"10.1371\/journal.pone.0016114","article-title":"Improved survival, vascular differentiation and wound healing potential of stem cells co-cultured with endothelial cells","volume":"6","author":"Pedroso","year":"2011","journal-title":"PLoS One."},{"issue":"6","key":"2025011312202754100_CIT0020","doi-asserted-by":"crossref","first-page":"e99733","DOI":"10.1371\/journal.pone.0099733","article-title":"A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells","volume":"9","author":"Cecchelli","year":"2014","journal-title":"PLoS One."},{"issue":"24","key":"2025011312202754100_CIT0021","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1007\/s00018-016-2301-3","article-title":"Methylphenidate-triggered ROS generation promotes caveolae-mediated transcytosis via Rac1 signaling and c-Src-dependent caveolin-1 phosphorylation in human brain endothelial cells","volume":"73","author":"Coelho-Santos","year":"2016","journal-title":"Cell Mol Life Sci."},{"issue":"1","key":"2025011312202754100_CIT0022","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s13046-023-02886-9","article-title":"Unveiling the role of osteosarcoma-derived secretome in premetastatic lung remodelling","volume":"42","author":"Almeida","year":"2023","journal-title":"J Exp Clin Cancer Res."},{"issue":"1","key":"2025011312202754100_CIT0023","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41596-018-0082-x","article-title":"Single-pot, solid-phase-enhanced sample preparation for proteomics experiments","volume":"14","author":"Hughes","year":"2019","journal-title":"Nat Protocols."},{"issue":"8","key":"2025011312202754100_CIT0024","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/jcbfm.2015.59","article-title":"The TNF-\u03b1\/Nf-\u03ba B signaling pathway has a key role in methamphetamine\u2013induced blood\u2013brain barrier dysfunction","volume":"35","author":"Coelho-Santos","year":"2015","journal-title":"J Cereb Blood Flow Metab."},{"issue":"3","key":"2025011312202754100_CIT0025","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3892\/mmr.2013.1875","article-title":"The role of claudin\u20115 in blood\u2011brain barrier (BBB) and brain metastases","volume":"9","author":"Jia","year":"2014","journal-title":"Mol Med Rep."},{"issue":"11","key":"2025011312202754100_CIT0026","doi-asserted-by":"crossref","first-page":"C955","DOI":"10.1152\/ajpcell.00326.2015","article-title":"Structural ECM components in the premetastatic and metastatic niche","volume":"310","author":"H\u00f8ye","year":"2016","journal-title":"Am J Physiol Cell Physiol."},{"key":"2025011312202754100_CIT0027","first-page":"3","article-title":"Exosomes: Key mediators of metastasis and pre-metastatic niche formation","volume-title":"Semin Cell Dev Biol","author":"Lobb","year":"2017"},{"issue":"1","key":"2025011312202754100_CIT0028","first-page":"229","article-title":"IGF2: A role in metastasis and tumor evasion from immune surveillance","volume":"11","author":"Belfiore","year":"2023","journal-title":"Biomed"},{"issue":"4","key":"2025011312202754100_CIT0029","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/abbs\/gmaa004","article-title":"HER4 promotes the growth and metastasis of osteosarcoma via the PI3K\/AKT pathway","volume":"52","author":"Li","year":"2020","journal-title":"Acta Biochim Biophys Sin."},{"key":"2025011312202754100_CIT0030","first-page":"93","article-title":"Proteomic approaches to decipher cancer cell secretome","volume-title":"Semin Cell Dev Biol","author":"Brandi","year":"2018"},{"issue":"11","key":"2025011312202754100_CIT0031","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1016\/j.bbapap.2013.01.039","article-title":"Bioinformatics tools for secretome analysis","volume":"1834","author":"Caccia","year":"2013","journal-title":"Biochim Biophys Acta."},{"issue":"4","key":"2025011312202754100_CIT0032","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41587-019-0036-z","article-title":"SignalP 5.0 improves signal peptide predictions using deep neural networks","volume":"37","author":"Almagro Armenteros","year":"2019","journal-title":"Nat Biotechnol."},{"issue":"1","key":"2025011312202754100_CIT0033","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2180-5-58","article-title":"Non-classical protein secretion in bacteria","volume":"5","author":"Bendtsen","year":"2005","journal-title":"BMC Microbiol."},{"issue":"1","key":"2025011312202754100_CIT0034","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/s12859-021-04219-z","article-title":"Prediction of unconventional protein secretion by exosomes","volume":"22","author":"Ras-Carmona","year":"2021","journal-title":"BMC Bioinf."},{"issue":"22","key":"2025011312202754100_CIT0035","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.3390\/molecules24224192","article-title":"ENPP1, an old enzyme with new functions, and small molecule inhibitors\u2014a STING in the tale of ENPP1","volume":"24","author":"Onyedibe","year":"2019","journal-title":"Molecules."},{"issue":"7","key":"2025011312202754100_CIT0036","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s11095-021-03131-8","article-title":"Effect of insulin receptor-knockdown on the expression levels of blood\u2013brain barrier functional proteins in human brain microvascular endothelial cells","volume":"39","author":"Nagano","year":"2022","journal-title":"Pharm Res."},{"issue":"9","key":"2025011312202754100_CIT0037","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1016\/j.xphs.2017.04.036","article-title":"Regulation of tight-junction integrity by insulin in an in vitro model of human blood\u2013brain barrier","volume":"106","author":"Ito","year":"2017","journal-title":"J Pharm Sci."},{"issue":"2","key":"2025011312202754100_CIT0038","doi-asserted-by":"crossref","first-page":"e55972","DOI":"10.1371\/journal.pone.0055972","article-title":"Inhibition of glycogen synthase kinase 3\u03b2 promotes tight junction stability in brain endothelial cells by half-life extension of occludin and claudin-5","volume":"8","author":"Ramirez","year":"2013","journal-title":"PLoS One."},{"key":"2025011312202754100_CIT0039","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.brainresbull.2020.08.032","article-title":"XQ-1H regulates Wnt\/GSK3\u03b2\/\u03b2-catenin pathway and ameliorates the integrity of blood brain barrier in mice with acute ischemic stroke","volume":"164","author":"Fei","year":"2020","journal-title":"Brain Res Bull."},{"issue":"2","key":"2025011312202754100_CIT0040","doi-asserted-by":"crossref","first-page":"55","DOI":"10.21037\/atm-21-5619","article-title":"Activation of the AKT\/GSK-3\u03b2\/\u03b2-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage","volume":"10","author":"Liao","year":"2022","journal-title":"Ann Transl Med"},{"key":"2025011312202754100_CIT0041","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.addr.2019.11.009","article-title":"The blood-brain barrier: Physiology and strategies for drug delivery","volume":"165-166","author":"Pandit","year":"2020","journal-title":"Adv Drug Deliv Rev."},{"issue":"5","key":"2025011312202754100_CIT0042","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1158\/2159-8290.CD-20-0387","article-title":"Metastasis and immune evasion from extracellular cGAMP hydrolysis","volume":"11","author":"Li","year":"2021","journal-title":"Cancer Discov"},{"issue":"21","key":"2025011312202754100_CIT0043","doi-asserted-by":"crossref","first-page":"e2119189119","DOI":"10.1073\/pnas.2119189119","article-title":"ENPP1\u2019s regulation of extracellular cGAMP is a ubiquitous mechanism of attenuating STING signaling","volume":"119","author":"Carozza","year":"2022","journal-title":"Proc Natl Acad Sci USA."},{"issue":"9","key":"2025011312202754100_CIT0044","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1158\/2326-6066.CIR-22-0140","article-title":"HER2\u2206 16 Engages ENPP1 to promote an immune cold microenvironment in breast cancer","volume":"11","author":"Attalla","year":"2023","journal-title":"Cancer Immunol Res"},{"issue":"6","key":"2025011312202754100_CIT0045","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1177\/1479164113500680","article-title":"Cellular and molecular mechanisms of endothelial dysfunction in diabetes","volume":"10","author":"Roberts","year":"2013","journal-title":"Diab Vasc Dis Res."},{"key":"2025011312202754100_CIT0046","doi-asserted-by":"crossref","first-page":"636174","DOI":"10.3389\/fpsyt.2021.636174","article-title":"Insulin resistance and blood-brain barrier dysfunction underlie neuroprogression in bipolar disorder","volume":"12","author":"Calkin","year":"2021","journal-title":"Front Psychiatry."},{"key":"2025011312202754100_CIT0047","doi-asserted-by":"crossref","first-page":"S623","DOI":"10.1016\/j.annonc.2023.09.2164","article-title":"1025MO Preliminary safety, pharmacokinetics and immunomodulatory activity of RBS2418, an oral ENPP1 inhibitor, alone and in combination with pembrolizumab in patients with solid tumors","volume":"34","author":"Marron","year":"2023","journal-title":"Ann Oncol."},{"key":"2025011312202754100_CIT0048","doi-asserted-by":"crossref","first-page":"116211","DOI":"10.1016\/j.ejmech.2024.116211","article-title":"Ecto-nucleotide pyrophosphatase\/phosphodiesterase 1 inhibitors: Research progress and prospects","volume":"267","author":"Guan","year":"2024","journal-title":"Eur J Med Chem."}],"container-title":["Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/advance-article-pdf\/doi\/10.1093\/neuonc\/noae169\/58967431\/noae169.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article-pdf\/27\/1\/167\/59766073\/noae169.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article-pdf\/27\/1\/167\/59766073\/noae169.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T12:21:56Z","timestamp":1736770916000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article\/27\/1\/167\/7745486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,30]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,8,30]]},"published-print":{"date-parts":[[2025,1,12]]}},"URL":"https:\/\/doi.org\/10.1093\/neuonc\/noae169","relation":{},"ISSN":["1522-8517","1523-5866"],"issn-type":[{"value":"1522-8517","type":"print"},{"value":"1523-5866","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,8,30]]}}}