The role of NTS/NTSR1 signal in pancreatic cancer progression
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ABSTRACT: Pancreatic cancer is one of the uncurable cancers and 5-year survival rate is still under 10 %. Therefore, it is urgent to identify a new molecular target for cure. In this study, the mouse serial transplantations by pancreatic orthotopic inoculation model were utilized for screening of new targets. The gene expression of highly malignant cancer cell lines, established in our previous study, showed increased expression of neurotensin receptor-1 (NTSR1). Re-analysis of clinical databases revealed that its expression was higher in pancreatic cancer dependent upon its stage. Overexpression of NTSR1 in SUIT-2 and Panc-1 cells accelerated tumorigenic and metastatic ability in vivo. RNA-sequence analysis revealed that MAPK and NF-kB signaling pathway were activated with neurotensin (NTS) stimulation in highly malignant cancer cell lines from Panc-1 cells. Moreover, NTS induced not only MMP-9, but also CTGF and other pro-inflammatory cytokines and chemokines. Administration of SR48692, a selective antagonist for NTSR1, suppressed tumorigenicity in vivo. These data suggested that NTSR1 can be a diagnostic marker and a new molecular target for pancreatic cancer treatment.
ORGANISM(S): Homo sapiens
PROVIDER: GSE147159 | GEO | 2020/10/28
REPOSITORIES: GEO
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