Targeting the Npy/Npy1r Signaling Axis in Mutant p53 Driven Pancreatic Cancer Impairs Metastasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1194985 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31630844_1.fastq.gz | Fastqsanger.gz | |||
| SRR31630844_2.fastq.gz | Fastqsanger.gz | |||
| SRR31630845_1.fastq.gz | Fastqsanger.gz | |||
| SRR31630845_2.fastq.gz | Fastqsanger.gz | |||
| SRR31630846_1.fastq.gz | Fastqsanger.gz |
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Project description:Pancreatic Cancer (PC) is a highly metastatic malignancy. Over 80% of PC patients present with advanced-stage disease, preventing potentially curative surgery. The Neuropeptide Y (NPY)system, best known for its role in controling energy homeostasis, has also been show to promote tumorigenesis in a range of cancer types, but its role in PC has yet to be explored. Here, we show that expression of NPY and NPY1R are upregulated in mouse PC models and human PC patients. Moreover, using the genetically engineered, autochthonous KPR172HC mouse model of PC we demonstrate that pancreas-specific and whole-body knockout of Npy1r significantly decreases metastasis to the liver. We identify that treatment with the NPY1R antagonist BIBO330485 significantly reduces KPR172HC migratory capacity on cell-derived matrices. Importantly, pharmacological NPY1R inhibition in an intrasplenic model of PC metastasis recapitulated the results of our genetic studies, with BIBO3304 significantly decreasing metastasis in the liver. Together, our results reveal that NPY/NPY1R signaling is a novel anti-metastatic target in PC.
2025-05-07 | PXD058833 | Pride
Project description:Pancreatic cancer (PC) is a highly metastatic malignancy. More than 80% of patients with PC present with advanced-stage disease, preventing potentially curative surgery. The neuropeptide Y (NPY) system, best known for its role in controlling energy homeostasis, has also been shown to promote tumorigenesis in a range of cancer types, but its role in PC has yet to be explored. We show that expression of NPY and NPY1R are up-regulated in mouse PC models and human patients with PC. Moreover, using the genetically engineered, autochthonous KPR172HC mouse model of PC, we demonstrate that pancreas-specific and whole-body knockout of Npy1r significantly decreases metastasis to the liver. We identify that treatment with the NPY1R antagonist BIBO3304 significantly reduces KPR172HC migratory capacity on cell-derived matrices. Pharmacological NPY1R inhibition in an intrasplenic model of PC metastasis recapitulated the results of our genetic studies, with BIBO3304 significantly decreasing liver metastasis. Together, our results reveal that NPY/NPY1R signaling is a previously unidentified antimetastatic target in PC.
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Project description:The TP53 transcription factor is frequently mutated at later stages of epithelial cancers, indicating a possible role in their invasion and metastasis. Importantly, in most cases rather than a simple loss of function p53 mutation, point mutations of p53 accumulate at the protein level and may have dominant negative functions. This study analyses gene expression differences between mice harbouring p53 mutation who do and do not develop metastasis.
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