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Open AccessArticle

The YAP1–NMU Axis Is Associated with Pancreatic Cancer Progression and Poor Outcome: Identification of a Novel Diagnostic Biomarker and Therapeutic Target

1
Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
2
Industrial Bio-Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
3
Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea
4
Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
5
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
6
National Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology, Jeonbuk 56212, Korea
7
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Songpa-gu, Seoul 05505, Korea
8
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(10), 1477; https://doi.org/10.3390/cancers11101477
Received: 12 August 2019 / Revised: 11 September 2019 / Accepted: 27 September 2019 / Published: 30 September 2019
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–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–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. View Full-Text
Keywords: pancreatic cancer; YAP1–NMU axis; metastasis; poor outcome pancreatic cancer; YAP1–NMU axis; metastasis; poor outcome
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Yoo, W.; Lee, J.; Jun, E.; Noh, K.H.; Lee, S.; Jung, D.; Jung, K.H.; Kim, J.-S.; Park, Y.-Y.; Kim, S.C.; Kim, S. The YAP1–NMU Axis Is Associated with Pancreatic Cancer Progression and Poor Outcome: Identification of a Novel Diagnostic Biomarker and Therapeutic Target. Cancers 2019, 11, 1477.

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