Neuron-derived Neurotensin Promotes Pancreatic Cancer Invasiveness and Gemcitabine Resistance Via the NTSR1/Akt Pathway

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2024 Mar 8

PMID 38455426

Authors

Yu-Hsuan Hung

Hui-Ching Wang

Shih-Han Hsu

Li-Yun Wang

Ya-Li Tsai

Yung-Yeh Su

Wen-Chun Hung

Li-Tzong Chen

Affiliations

Soon will be listed here.

Abstract

Perineural invasion and neurogenesis are frequently observed in pancreatic ductal adenocarcinoma (PDAC) and link to poor outcome. However, how neural factors affect PDAC prognosis and the underlying mechanism as well as counteracting therapeutic are still unclear. systematic analysis was performed with PROGgene to identify potential neural factor and its receptor in pancreatic cancer. assays including migration, invasion, 3D recruitment, and gemcitabine resistance were performed to study the effect of neuron-derived neurotensin (NTS) on pancreatic cancer behavior. Orthotopic animal study was used to validate the findings. Gene set enrichment analysis (GSEA) was performed to confirm the results from to . Expression of NTS and its receptor 1 (NTSR1) predicted poor prognosis in PDAC. NTS synthetic peptide or neuron-derived condition medium promoted pancreatic cancer invasiveness and recruitment in 2D and 3D assays. NTS-induced effects depended on NTSR1 and PI3K activation. GDC-0941, a clinically approved PI3K inhibitor, counteracted NTS-induced effects . Inhibition of NTSR1 in pancreatic cancer cells resulted in decreased tumor dissemination and diminished PI3K activation . NTS boosted gemcitabine resistance via NTSR1 in pancreatic cancer. Our results suggest that neural cell-secreted NTS plays an important role in promoting PDAC.

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