{"data":{"id":"10.5061/dryad.7sqv9s52d","type":"dois","attributes":{"doi":"10.5061/dryad.7sqv9s52d","prefix":"10.5061","suffix":"dryad.7sqv9s52d","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Sela Peremen, Liav","nameType":"Personal","givenName":"Liav","familyName":"Sela Peremen","affiliation":["Tel Aviv University"],"nameIdentifiers":[]},{"name":"Telerman, Alona","nameType":"Personal","givenName":"Alona","familyName":"Telerman","affiliation":["Sheba Medical Center"],"nameIdentifiers":[]},{"name":"Kahan Yossef, Yuval","nameType":"Personal","givenName":"Yuval","familyName":"Kahan Yossef","affiliation":["Tel Aviv University"],"nameIdentifiers":[]},{"name":"Peshes Yaloz, Naama","nameType":"Personal","givenName":"Naama","familyName":"Peshes Yaloz","affiliation":["Sheba Medical Center"],"nameIdentifiers":[]},{"name":"Tirosh, Amit","nameType":"Personal","givenName":"Amit","familyName":"Tirosh","affiliation":["Sheba Medical Center"],"nameIdentifiers":[{"schemeUri":"https://orcid.org","nameIdentifier":"https://orcid.org/0000-0003-3794-9634","nameIdentifierScheme":"ORCID"}]}],"titles":[{"title":"Targeted netrin inhibition disrupts DCC-dependent pathways and suppresses xenograft growth in neuroendocrine neoplasms"}],"publisher":"Dryad","container":{},"publicationYear":2025,"subjects":[{"subject":"FOS: Basic medicine","schemeUri":"https://web-archive.oecd.org/2012-06-15/138575-38235147.pdf","subjectScheme":"fos"},{"subject":"FOS: Basic medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"DCC"},{"subject":"Netrin"},{"subject":"neuroendocrine"}],"contributors":[],"dates":[{"date":"2024-09-20T14:49:12Z","dateType":"Created"},{"date":"2024-09-20T14:49:18Z","dateType":"Submitted"},{"date":"2025-10-29T00:00:00Z","dateType":"Issued"},{"date":"2025-10-29T00:00:00Z","dateType":"Available"}],"language":"en","types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsCitedBy","relatedIdentifier":"10.1530/erc-25-0226","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["1813377 bytes"],"formats":[],"version":"5","rightsList":[{"rights":"Creative Commons Zero v1.0 Universal","rightsUri":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc0-1.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"DCC functions as a tumor suppressor and is altered in various tumors,\n including neuroendocrine neoplasms. Netrin (NTN)-1 serves as the primary\n ligand for DCC. Operating as a dependence receptor, DCC induces apoptosis\n without NTN and promotes cell survival in its presence. In specific\n cancers like small-cell lung cancer and neuroblastoma, upregulation of\n NTN-3 rather than NTN-1 has been observed. However, the precise\n involvement of NTNs and DCC in PNEN remains unclear. We assessed DCC and\n netrin expression in pancreatic neuroendocrine neoplasms (PNEN) cells\n (BON-1). We examined netrin's effect on cell viability using DCC\n knockdown and NP137, a netrin-inhibiting antibody. In vivo, PNEN cells\n were injected into nude mice and treated with NP137 or PBS. Tumor RNA\n sequencing was performed. A population-based analysis using TCGA data\n evaluated DCC and NTN3 expression on survival. BON-1 cells exhibited\n elevated expression of DCC and NTN-3. The addition of NTN-1 augmented BON1\n viability, a response lessened upon NTN blockade using NP137. Furthermore,\n DCC siRNA negated the effect of NTN-1 on cell viability. Mice bearing PNEN\n BON-1 xenografts and treated with NP137 exhibited markedly diminished\n xenograft growth. RNA sequencing revealed upregulation of small nucleolar\n RNAs (SNORs) in NP137-treated tumors, with enriched pathways related to\n RNA processing. TCGA analysis showed a negative correlation between NTN3\n expression and survival. Our data suggest that NTN-3, NTN-1, and DCC play\n co-dependent oncogenic roles in PNENs that are reversible by inhibiting\n NTN binding to DCC. NTN inhibition merits further investigation as a\n potential therapeutic target.","descriptionType":"Abstract"},{"description":"# Targeted netrin inhibition disrupts DCC-dependent pathways and\n suppresses xenograft growth in neuroendocrine neoplasms\n [https://doi.org/10.5061/dryad.7sqv9s52d](https://doi.org/10.5061/dryad.7sqv9s52d) ## Description of the data and file structure In vivo, BON1 (PNEN) cells were injected into nude mice and treated with NP137 or PBS. Tumor RNA sequencing was performed. The following .counts files for gene expression analysis are available: **Treated with NP137:**\\ Netrin_01.fqAligned.sortedByCoord.out.bam.counts Netrin_11.fqAligned.sortedByCoord.out.bam.counts Netrin_16.fqAligned.sortedByCoord.out.bam.counts **Treated with PBS:**\\ Netrin_17.fqAligned.sortedByCoord.out.bam.counts Netrin_18.fqAligned.sortedByCoord.out.bam.counts ## Code/software DESEQ2 package on R Studio, based on the main pipeline parameters.","descriptionType":"TechnicalInfo"}],"geoLocations":[],"fundingReferences":[],"xml":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zOnhzaT0iaHR0cDovL3d3dy53My5vcmcvMjAwMS9YTUxTY2hlbWEtaW5zdGFuY2UiIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00L21ldGFkYXRhLnhzZCI+CiAgPGlkZW50aWZpZXIgaWRlbnRpZmllclR5cGU9IkRPSSI+MTAuNTA2MS9EUllBRC43U1FWOVM1MkQ8L2lkZW50aWZpZXI+CiAgPGNyZWF0b3JzPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZSBuYW1lVHlwZT0iUGVyc29uYWwiPlNlbGEgUGVyZW1lbiwgTGlhdjwvY3JlYXRvck5hbWU+CiAgICAgIDxhZmZpbGlhdGlvbiBhZmZpbGlhdGlvbklkZW50aWZpZXI9Imh0dHBzOi8vcm9yLm9yZy8wNG1oemd4NDkiIGFmZmlsaWF0aW9uSWRlbnRpZmllclNjaGVtZT0iUk9SIiBzY2hlbWVVUkk9Imh0dHBzOi8vcm9yLm9yZyI+VGVsIEF2aXYgVW5pdmVyc2l0eTwvYWZmaWxpYXRpb24+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lIG5hbWVUeXBlPSJQZXJzb25hbCI+VGVsZXJtYW4sIEFsb25hPC9jcmVhdG9yTmFtZT4KICAgICAgPGFmZmlsaWF0aW9uIGFmZmlsaWF0aW9uSWRlbnRpZmllcj0iaHR0cHM6Ly9yb3Iub3JnLzAyMHJ6eDQ4NyIgYWZmaWxpYXRpb25JZGVudGlmaWVyU2NoZW1lPSJST1IiIHNjaGVtZVVSST0iaHR0cHM6Ly9yb3Iub3JnIj5TaGViYSBNZWRpY2FsIENlbnRlcjwvYWZmaWxpYXRpb24+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lIG5hbWVUeXBlPSJQZXJzb25hbCI+S2FoYW4gWW9zc2VmLCBZdXZhbDwvY3JlYXRvck5hbWU+CiAgICAgIDxhZmZpbGlhdGlvbiBhZmZpbGlhdGlvbklkZW50aWZpZXI9Imh0dHBzOi8vcm9yLm9yZy8wNG1oemd4NDkiIGFmZmlsaWF0aW9uSWRlbnRpZmllclNjaGVtZT0iUk9SIiBzY2hlbWVVUkk9Imh0dHBzOi8vcm9yLm9yZyI+VGVsIEF2aXYgVW5pdmVyc2l0eTwvYWZmaWxpYXRpb24+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lIG5hbWVUeXBlPSJQZXJzb25hbCI+UGVzaGVzIFlhbG96LCBOYWFtYTwvY3JlYXRvck5hbWU+CiAgICAgIDxhZmZpbGlhdGlvbiBhZmZpbGlhdGlvbklkZW50aWZpZXI9Imh0dHBzOi8vcm9yLm9yZy8wMjByeng0ODciIGFmZmlsaWF0aW9uSWRlbnRpZmllclNjaGVtZT0iUk9SIiBzY2hlbWVVUkk9Imh0dHBzOi8vcm9yLm9yZyI+U2hlYmEgTWVkaWNhbCBDZW50ZXI8L2FmZmlsaWF0aW9uPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZSBuYW1lVHlwZT0iUGVyc29uYWwiPlRpcm9zaCwgQW1pdDwvY3JlYXRvck5hbWU+CiAgICAgIDxuYW1lSWRlbnRpZmllciBuYW1lSWRlbnRpZmllclNjaGVtZT0iT1JDSUQiIHNjaGVtZVVSST0iaHR0cDovL29yY2lkLm9yZy8iPjAwMDAtMDAwMy0zNzk0LTk2MzQ8L25hbWVJZGVudGlmaWVyPgogICAgICA8YWZmaWxpYXRpb24gYWZmaWxpYXRpb25JZGVudGlmaWVyPSJodHRwczovL3Jvci5vcmcvMDIwcnp4NDg3IiBhZmZpbGlhdGlvbklkZW50aWZpZXJTY2hlbWU9IlJPUiIgc2NoZW1lVVJJPSJodHRwczovL3Jvci5vcmciPlNoZWJhIE1lZGljYWwgQ2VudGVyPC9hZmZpbGlhdGlvbj4KICAgIDwvY3JlYXRvcj4KICA8L2NyZWF0b3JzPgogIDx0aXRsZXM+CiAgICA8dGl0bGU+CiAgICAgIFRhcmdldGVkIG5ldHJpbiBpbmhpYml0aW9uIGRpc3J1cHRzIERDQy1kZXBlbmRlbnQgcGF0aHdheXMgYW5kIHN1cHByZXNzZXMKICAgICAgeGVub2dyYWZ0IGdyb3d0aCBpbiBuZXVyb2VuZG9jcmluZSBuZW9wbGFzbXMKICAgIDwvdGl0bGU+CiAgPC90aXRsZXM+CiAgPHB1Ymxpc2hlciBwdWJsaXNoZXJJZGVudGlmaWVyPSJodHRwczovL3Jvci5vcmcvMDB4Nmg1bjk1IiBwdWJsaXNoZXJJZGVudGlmaWVyU2NoZW1lPSJST1IiIHNjaGVtZVVSST0iaHR0cHM6Ly9yb3Iub3JnLyI+RHJ5YWQ8L3B1Ymxpc2hlcj4KICA8cmVzb3VyY2VUeXBlIHJlc291cmNlVHlwZUdlbmVyYWw9IkRhdGFzZXQiPmRhdGFzZXQ8L3Jlc291cmNlVHlwZT4KICA8cHVibGljYXRpb25ZZWFyPjIwMjU8L3B1YmxpY2F0aW9uWWVhcj4KICA8c3ViamVjdHM+CiAgICA8c3ViamVjdCBzdWJqZWN0U2NoZW1lPSJmb3MiIHNjaGVtZVVSST0iaHR0cHM6Ly93ZWItYXJjaGl2ZS5vZWNkLm9yZy8yMDEyLTA2LTE1LzEzODU3NS0zODIzNTE0Ny5wZGYiPkZPUzogQmFzaWMgbWVkaWNpbmU8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5EQ0M8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5OZXRyaW48L3N1YmplY3Q+CiAgICA8c3ViamVjdD5uZXVyb2VuZG9jcmluZTwvc3ViamVjdD4KICA8L3N1YmplY3RzPgogIDxkYXRlcz4KICAgIDxkYXRlIGRhdGVUeXBlPSJDcmVhdGVkIj4yMDI0LTA5LTIwVDE0OjQ5OjEyWjwvZGF0ZT4KICAgIDxkYXRlIGRhdGVUeXBlPSJTdWJtaXR0ZWQiPjIwMjQtMDktMjBUMTQ6NDk6MThaPC9kYXRlPgogICAgPGRhdGUgZGF0ZVR5cGU9Iklzc3VlZCI+MjAyNS0xMC0yOVQwMDowMDowMFo8L2RhdGU+CiAgICA8ZGF0ZSBkYXRlVHlwZT0iQXZhaWxhYmxlIj4yMDI1LTEwLTI5VDAwOjAwOjAwWjwvZGF0ZT4KICA8L2RhdGVzPgogIDxsYW5ndWFnZT5lbjwvbGFuZ3VhZ2U+CiAgPHJlbGF0ZWRJZGVudGlmaWVycz4KICAgIDxyZWxhdGVkSWRlbnRpZmllciByZWxhdGlvblR5cGU9IklzQ2l0ZWRCeSIgcmVsYXRlZElkZW50aWZpZXJUeXBlPSJET0kiPmh0dHBzOi8vZG9pLm9yZy8xMC4xNTMwL0VSQy0yNS0wMjI2PC9yZWxhdGVkSWRlbnRpZmllcj4KICA8L3JlbGF0ZWRJZGVudGlmaWVycz4KICA8c2l6ZXM+CiAgICA8c2l6ZT4xODEzMzc3IGJ5dGVzPC9zaXplPgogIDwvc2l6ZXM+CiAgPHZlcnNpb24+NTwvdmVyc2lvbj4KICA8cmlnaHRzTGlzdD4KICAgIDxyaWdodHMgcmlnaHRzVVJJPSJodHRwczovL3NwZHgub3JnL2xpY2Vuc2VzL0NDMC0xLjAuaHRtbCI+Q3JlYXRpdmUgQ29tbW9ucyBaZXJvIHYxLjAgVW5pdmVyc2FsPC9yaWdodHM+CiAgPC9yaWdodHNMaXN0PgogIDxkZXNjcmlwdGlvbnM+CiAgICA8ZGVzY3JpcHRpb24gZGVzY3JpcHRpb25UeXBlPSJBYnN0cmFjdCI+CiAgICAgIERDQyBmdW5jdGlvbnMgYXMgYSB0dW1vciBzdXBwcmVzc29yIGFuZCBpcyBhbHRlcmVkIGluIHZhcmlvdXMgdHVtb3JzLAogICAgICBpbmNsdWRpbmcgbmV1cm9lbmRvY3JpbmUgbmVvcGxhc21zLiBOZXRyaW4gKE5UTiktMSBzZXJ2ZXMgYXMgdGhlIHByaW1hcnkKICAgICAgbGlnYW5kIGZvciBEQ0MuIE9wZXJhdGluZyBhcyBhIGRlcGVuZGVuY2UgcmVjZXB0b3IsIERDQyBpbmR1Y2VzIGFwb3B0b3NpcwogICAgICB3aXRob3V0IE5UTiBhbmQgcHJvbW90ZXMgY2VsbCBzdXJ2aXZhbCBpbiBpdHMgcHJlc2VuY2UuIEluIHNwZWNpZmljCiAgICAgIGNhbmNlcnMgbGlrZSBzbWFsbC1jZWxsIGx1bmcgY2FuY2VyIGFuZCBuZXVyb2JsYXN0b21hLCB1cHJlZ3VsYXRpb24gb2YKICAgICAgTlROLTMgcmF0aGVyIHRoYW4gTlROLTEgaGFzIGJlZW4gb2JzZXJ2ZWQuIEhvd2V2ZXIsIHRoZSBwcmVjaXN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