Targeted netrin inhibition disrupts DCC-dependent pathways and suppresses xenograft growth in neuroendocrine neoplasms

DCC functions as a tumor suppressor and is altered in various tumors, including neuroendocrine neoplasms. 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). 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 respo..., , , # Targeted netrin inhibition disrupts DCC-dependent pathways and suppresses xenograft growth in neuroendocrine neoplasms

[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.,