論文

査読有り 本文へのリンクあり 国際誌
2021年1月

Neurotensin receptor 1 signaling promotes pancreatic cancer progression

Molecular Oncology
  • Kei Takahashi
  • ,
  • Shogo Ehata
  • ,
  • Kensuke Miyauchi
  • ,
  • Yasuyuki Morishita
  • ,
  • Keiji Miyazawa
  • ,
  • Kohei Miyazono

15
1
開始ページ
151
終了ページ
166
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/1878-0261.12815

Pancreatic cancer is one of the cancers with the poorest prognosis, with a 5-year survival rate of approximately 5–10%. Thus, it is urgent to identify molecular targets for the treatment of pancreatic cancer. Using serial transplantations in a mouse pancreatic orthotopic inoculation model, we previously produced highly malignant pancreatic cancer sublines with increased tumor-forming abilities in vivo. Here, we used these sublines to screen molecular targets for the treatment of pancreatic cancer. Among the genes with increased expression levels in the sublines, we focused on those encoding cell surface receptors that may be involved in the interactions between cancer cells and the tumor microenvironment. Based on our previous RNA-sequence analysis, we found increased expression levels of neurotensin (NTS) receptor 1 (NTSR1) in highly malignant pancreatic cancer sublines. Furthermore, re-analysis of clinical databases revealed that the expression level of NTSR1 was increased in advanced pancreatic cancer and that high NTSR1 levels were correlated with a poor prognosis. Overexpression of NTSR1 in human pancreatic cancer cells Panc-1 and SUIT-2 accelerated their tumorigenic and metastatic abilities in vivo. In addition, RNA-sequence analysis showed that MAPK and NF-κB signaling pathways were activated upon NTS stimulation in highly malignant cancer sublines and also revealed many new target genes for NTS in pancreatic cancer cells. NTS stimulation increased the expression of MMP-9 and other pro-inflammatory cytokines and chemokines in pancreatic cancer cells. Moreover, the treatment with SR48692, a selective NTSR1 antagonist, suppressed the activation of the MAPK and NF-κB signaling pathways and induction of target genes in pancreatic cancer cells in vitro, while the administration of SR48692 attenuated the tumorigenicity of pancreatic cancer cells in vivo. These findings suggest that NTSR1 may be a prognostic marker and a molecular target for pancreatic cancer treatment.

リンク情報
DOI
https://doi.org/10.1002/1878-0261.12815
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33034134
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782081
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85096771971&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85096771971&origin=inward
ID情報
  • DOI : 10.1002/1878-0261.12815
  • ISSN : 1574-7891
  • eISSN : 1878-0261
  • PubMed ID : 33034134
  • PubMed Central 記事ID : PMC7782081
  • SCOPUS ID : 85096771971

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