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The YAP1–NMU Axis Is Associated with Pancreatic Cancer Progression and Poor Outcome: Identification of a Novel Diagnostic Biomarker and Therapeutic Target
- Source :
- Cancers, Vol 11, Iss 10, p 1477 (2019), Cancers, Volume 11, Issue 10
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Yes-associated protein (YAP)-1 is highly upregulated in pancreatic cancer and associated with tumor progression. However, little is known about the role of YAP1 and related genes in pancreatic cancer. Here, we identified target genes regulated by YAP1 and explored their role in pancreatic cancer progression and the related clinical implications. Analysis of different pancreatic cancer databases showed that Neuromedin U (NMU) expression was positively correlated with YAP1 expression in the tumor group. The Cancer Genome Atlas data indicated that high YAP1 and NMU expression levels were associated with poor mean and overall survival. YAP1 overexpression induced NMU expression and transcription and promoted cell motility in vitro and tumor metastasis in vivo via upregulation of epithelial&ndash<br />mesenchymal transition (EMT), whereas specific inhibition of NMU in cells stably expressing YAP1 had the opposite effect in vitro and in vivo. To define this functional association, we identified a transcriptional enhanced associate domain (TEAD) binding site in the NMU promoter and demonstrated that YAP1&ndash<br />TEAD binding upstream of the NMU gene regulated its transcription. These results indicate that the identified positive correlation between YAP1 and NMU is a potential novel drug target and biomarker in metastatic pancreatic cancer.
- Subjects :
- 0301 basic medicine
Cancer Research
yap1–nmu axis
pancreatic cancer
Biology
lcsh:RC254-282
Article
Metastasis
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
In vivo
Transcription (biology)
Pancreatic cancer
medicine
metastasis
YAP1
poor outcome
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
030104 developmental biology
Oncology
Tumor progression
030220 oncology & carcinogenesis
Cancer research
Neuromedin U
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....86b2320259e701375523ae293b6cf482