Data · dataset · 2025
Targeted netrin inhibition disrupts DCC-dependent pathways and suppresses xenograft growth in neuroendocrine neoplasms
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DCC functions as a tumor suppressor and is altered in various tumors, including neuroendocrine neoplasms.
Description
Netrin (NTN)-1 serves as the primary ligand for DCC. Operating as a dependence receptor, DCC induces apoptosis without NTN and promotes cell survival in its presence.
In specific cancers like small-cell lung cancer and neuroblastoma, upregulation of NTN-3 rather than NTN-1 has been observed. However, the precise involvement of NTNs and DCC in PNEN remains unclear. We assessed DCC and netrin expression in pancreatic neuroendocrine neoplasms (PNEN) cells (BON-1).
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We examined netrin's effect on cell viability using DCC knockdown and NP137, a netrin-inhibiting antibody. In vivo, PNEN cells were injected into nude mice and treated with NP137 or PBS. Tumor RNA sequencing was performed.
A population-based analysis using TCGA data evaluated DCC and NTN3 expression on survival. BON-1 cells exhibited elevated expression of DCC and NTN-3. The addition of NTN-1 augmented BON1 viability, a response lessened upon NTN blockade using NP137.
Furthermore, DCC siRNA negated the effect of NTN-1 on cell viability. Mice bearing PNEN BON-1 xenografts and treated with NP137 exhibited markedly diminished xenograft growth. RNA sequencing revealed upregulation of small nucleolar RNAs (SNORs) in NP137-treated tumors, with enriched pathways related to RNA processing.
TCGA analysis showed a negative correlation between NTN3 expression and survival. Our data suggest that NTN-3, NTN-1, and DCC play co-dependent oncogenic roles in PNENs that are reversible by inhibiting NTN binding to DCC. NTN inhibition merits further investigation as a potential therapeutic target.
Links
Where it is published
- Repository landing page datadryad.org/dataset/doi:10.5061/dryad.7sqv9s52d ↗
landing page · from DataCite
- DOI doi.org/10.5061/dryad.7sqv9s52d ↗
DOI / persistent id · from DataCite
Documentation and papers
- Creative Commons Zero v1.0 Universal creativecommons.org/publicdomain/zero/1.0/legalcode ↗
license · from DataCite
- IsCitedBy 10.1530/erc-25-0226 doi.org/10.1530/erc-25-0226 ↗
publication · from DataCite
Catalogue records · 2
- DataCite API api.datacite.org/dois/10.5061/dryad.7sqv9s52d ↗
metadata API · from DataCite
- DataCite Commons commons.datacite.org/doi.org/10.5061/dryad.7sqv9s52d ↗
catalogue entry · from DataCite
Topics
- Stated by source
- Basic medicine
- Inferred from text
- Cancer 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 12 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| DataCite | 10.5061/dryad.7sqv9s52d | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| byte_size | source · DataCite | connector:datacite@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].fos:basic-medicine | source · DataCite | connector:datacite@1.0.0 | |
| concepts[modality].local:modality:rna-seq | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| created_date | source · DataCite | connector:datacite@1.0.0 | |
| description | source · DataCite | connector:datacite@1.0.0 | /data/attributes/descriptions |
| license | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| publication_date | source · DataCite | connector:datacite@1.0.0 | /data/attributes/dates |
| title | source · DataCite | connector:datacite@1.0.0 | /data/attributes/titles/0/title |
| version_label | source · DataCite | connector:datacite@1.0.0 |