{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T23:37:34Z","timestamp":1777765054937,"version":"3.51.4"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang Province Natural Science Foundation","doi-asserted-by":"publisher","award":["ZCLQN25H1003"],"award-info":[{"award-number":["ZCLQN25H1003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004863","name":"Zhejiang Chinese Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004863","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular Signalling"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.cellsig.2025.112225","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T15:45:38Z","timestamp":1762703138000},"page":"112225","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["LRP1 regulates GDNF secretion and perineural invasion in pancreatic cancer via PI3K\/AKT signaling"],"prefix":"10.1016","volume":"138","author":[{"given":"Songmei","family":"Lou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shenhao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengli","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.cellsig.2025.112225_bb0005","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn812","article-title":"The GDNF family: signalling, biological functions and therapeutic value","volume":"3","author":"Airaksinen","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.cellsig.2025.112225_bb0010","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.semcancer.2019.07.009","article-title":"PI3K\/Akt\/mTOR inhibitors in cancer: at the bench and bedside","volume":"59","author":"Alzahrani","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.cellsig.2025.112225_bb0015","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/pros.1137","article-title":"In vitro dorsal root ganglia and human prostate cell line interaction: redefining perineural invasion in prostate cancer","volume":"49","author":"Ayala","year":"2001","journal-title":"Prostate"},{"key":"10.1016\/j.cellsig.2025.112225_bb0020","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13024-022-00560-w","article-title":"LRP1 is a neuronal receptor for \u03b1-synuclein uptake and spread","volume":"17","author":"Chen","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.cellsig.2025.112225_bb0025","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.3390\/cancers2031513","article-title":"Neural invasion in pancreatic cancer: the past, present and future","volume":"2","author":"Demir","year":"2010","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.cellsig.2025.112225_bb0030","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nrgastro.2015.166","article-title":"Neural plasticity in pancreatitis and pancreatic cancer","volume":"12","author":"Demir","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.cellsig.2025.112225_bb0035","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1080\/0284186X.2016.1197419","article-title":"More deaths from pancreatic cancer than breast cancer in the EU by 2017","volume":"55","author":"Ferlay","year":"2016","journal-title":"Acta Oncol."},{"key":"10.1016\/j.cellsig.2025.112225_bb0040","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.pan.2019.02.012","article-title":"Over-expression of low-density lipoprotein receptor-related Protein-1 is associated with poor prognosis and invasion in pancreatic ductal adenocarcinoma","volume":"19","author":"Gheysarzadeh","year":"2019","journal-title":"Pancreatology"},{"key":"10.1016\/j.cellsig.2025.112225_bb0045","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1111\/jcmm.15265","article-title":"NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K\/AKT\/GSK signal pathway","volume":"24","author":"Jiang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.cellsig.2025.112225_bb0050","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.pharmthera.2019.04.010","article-title":"Signaling in the microenvironment of pancreatic cancer: transmitting along the nerve","volume":"200","author":"Jurcak","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.cellsig.2025.112225_bb0055","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1053\/j.gastro.2019.05.065","article-title":"Axon guidance molecules promote Perineural invasion and metastasis of Orthotopic pancreatic tumors in mice","volume":"157","author":"Jurcak","year":"2019","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cellsig.2025.112225_bb0060","first-page":"2965","article-title":"Role of LRP1 in transport of CCN2 protein in chondrocytes","volume":"125","author":"Kawata","year":"2012","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.cellsig.2025.112225_bb0065","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/cac2.12188","article-title":"Cellular and molecular mechanisms of perineural invasion of pancreatic ductal adenocarcinoma","volume":"41","author":"Li","year":"2021","journal-title":"Cancer Commun. (Lond)"},{"key":"10.1016\/j.cellsig.2025.112225_bb0070","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.neuropharm.2010.10.012","article-title":"Exogenous gangliosides increase the release of brain-derived neurotrophic factor","volume":"60","author":"Lim","year":"2011","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.cellsig.2025.112225_bb0075","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.113691","article-title":"Perineural invasion-associated biomarkers for tumor development","volume":"155","author":"Liu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.cellsig.2025.112225_bb0080","doi-asserted-by":"crossref","first-page":"50250","DOI":"10.1074\/jbc.M309150200","article-title":"The low density lipoprotein receptor-related protein modulates protease activity in the brain by mediating the cellular internalization of both neuroserpin and neuroserpin-tissue-type plasminogen activator complexes","volume":"278","author":"Makarova","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cellsig.2025.112225_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.100842","article-title":"Molecular chaperone RAP interacts with LRP1 in a dynamic bivalent mode and enhances folding of ligand-binding regions of other LDLR family receptors","volume":"297","author":"Marakasova","year":"2021","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cellsig.2025.112225_bb0090","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41586-020-2156-5","article-title":"LRP1 is a master regulator of tau uptake and spread","volume":"580","author":"Rauch","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.cellsig.2025.112225_bb0095","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1073\/pnas.1512603113","article-title":"Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer","volume":"113","author":"Saloman","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.cellsig.2025.112225_bb0100","doi-asserted-by":"crossref","DOI":"10.1111\/nmo.13880","article-title":"Localisation analysis of nerves in the mouse pancreas reveals the sites of highest nerve density and nociceptive innervation","volume":"32","author":"Saricaoglu","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"10.1016\/j.cellsig.2025.112225_bb0105","article-title":"MIF promotes cell invasion by the LRP1-uPAR interaction in pancreatic cancer cells","volume":"12","author":"Sun","year":"2022","journal-title":"Front. Oncol."},{"key":"10.1016\/j.cellsig.2025.112225_bb0110","article-title":"Hallmarks of perineural invasion in pancreatic ductal adenocarcinoma: new biological dimensions","volume":"14","author":"Sun","year":"2024","journal-title":"Front. Oncol."},{"key":"10.1016\/j.cellsig.2025.112225_bb0115","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/00006676-200207000-00009","article-title":"Characterization of the neurotrophic response to acute pancreatitis","volume":"25","author":"Toma","year":"2002","journal-title":"Pancreas"},{"key":"10.1016\/j.cellsig.2025.112225_bb0120","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3389\/fphar.2015.00271","article-title":"The Matricellular receptor LRP1 forms an Interface for signaling and endocytosis in modulation of the extracellular tumor environment","volume":"6","author":"Van Gool","year":"2015","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.cellsig.2025.112225_bb0125","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.critrevonc.2017.02.005","article-title":"The role of perineural invasion in predicting survival in patients with primary operable colorectal cancer: a systematic review","volume":"112","author":"van Wyk","year":"2017","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"10.1016\/j.cellsig.2025.112225_bb0130","doi-asserted-by":"crossref","first-page":"5751","DOI":"10.2147\/OTT.S208924","article-title":"Oridonin overcomes the gemcitabine resistant PANC-1\/gem cells by regulating GST pi and LRP\/1 ERK\/JNK signalling","volume":"12","author":"Wang","year":"2019","journal-title":"Onco. Targets. Ther."},{"key":"10.1016\/j.cellsig.2025.112225_bb0135","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40880-015-0064-0","article-title":"Roles of low-density lipoprotein receptor-related protein 1 in tumors","volume":"35","author":"Xing","year":"2016","journal-title":"Chin. J. Cancer"},{"key":"10.1016\/j.cellsig.2025.112225_bb0140","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.canlet.2021.03.016","article-title":"CD74 promotes perineural invasion of cancer cells and mediates neuroplasticity via the AKT\/EGR-1\/GDNF axis in pancreatic ductal adenocarcinoma","volume":"508","author":"Zhang","year":"2021","journal-title":"Cancer Lett."},{"key":"10.1016\/j.cellsig.2025.112225_bb0145","doi-asserted-by":"crossref","DOI":"10.3892\/or.2022.8275","article-title":"High-glucose microenvironment promotes perineural invasion of pancreatic cancer via activation of hypoxia inducible factor 1\u03b1","volume":"47","author":"Zhang","year":"2022","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.cellsig.2025.112225_bb0150","doi-asserted-by":"crossref","first-page":"432","DOI":"10.3892\/ol.2023.14019","article-title":"LRP1 as a promising therapeutic target for gastrointestinal tumors: inhibiting proliferation, invasion and migration of cancer cells","volume":"26","author":"Zhu","year":"2023","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.cellsig.2025.112225_bb0155","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1200\/JCO.1999.17.8.2419","article-title":"Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer","volume":"17","author":"Zhu","year":"1999","journal-title":"J. Clin. Oncol."}],"container-title":["Cellular Signalling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656825006400?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656825006400?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T22:34:49Z","timestamp":1766097289000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0898656825006400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":31,"alternative-id":["S0898656825006400"],"URL":"https:\/\/doi.org\/10.1016\/j.cellsig.2025.112225","relation":{},"ISSN":["0898-6568"],"issn-type":[{"value":"0898-6568","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"LRP1 regulates GDNF secretion and perineural invasion in pancreatic cancer via PI3K\/AKT signaling","name":"articletitle","label":"Article Title"},{"value":"Cellular Signalling","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cellsig.2025.112225","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112225"}}