Wnt-11 Expression Promotes Invasiveness and Correlates with Survival in Human Pancreatic Ductal Adeno Carcinoma
by
Dafydd A. Dart 1,2
, Damla E Arisan 3, Sioned Owen 1,4, Chunyi Hao 5, Wen G. Jiang 1 and Pinar Uysal-Onganer 6,*
Dafydd A. Dart 1,2, Damla E Arisan 3, Sioned Owen 1,4, Chunyi Hao 5, Wen G. Jiang 1 and Pinar Uysal-Onganer 6,*
1
Cardiff China Medical Research Collaborative, Institute of Cancer and Genetics, Cardiff University Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK
2
Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK
3
Science and Literature Faculty, Department of Molecular Biology and Genetics, Istanbul Kultur University, Atakoy Campus, Istanbul 34156, Turkey
4
Alfred Russel Wallace Building, Upper Glyntaff, University of South Wales, Pontypridd CF37 4BD, UK
5
Beijing Cancer Institute and Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University School of Oncology, Beijing 100142, China
6
School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster,115 New Cavendish Street, London W1W 6UW, UK
*
Author to whom correspondence should be addressed.
Genes 2019, 10(11), 921; https://doi.org/10.3390/genes10110921
Received: 3 October 2019 / Revised: 26 October 2019 / Accepted: 5 November 2019 / Published: 11 November 2019
(This article belongs to the Special Issue Wnt Signaling in Development, Regeneration and Cancer)
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, proving difficult to manage clinically. Wnt-11, a developmentally regulated gene producing a secreted protein, has been associated with various carcinomas but has not previously been studied in PDAC. The present study aimed to elucidate these aspects first in vitro and then in a clinical setting in vivo. Molecular analyses of Wnt-11 expression as well as other biomarkers involved qRT-PCR, RNA-seq and siRNA. Proliferation was measured by MTT; invasiveness was quantified by Boyden chamber (Matrigel) assay. Wnt-11 mRNA was present in three different human PDAC cell lines. Wnt-11 loss affected epithelial-mesenchymal transition and expression of neuronal and stemness biomarkers associated with metastasis. Indeed, silencing Wnt-11 in Panc-1 cells significantly inhibited their Matrigel invasiveness without affecting their proliferative activity. Consistently with the in vitro data, human biopsies of PDAC showed significantly higher Wnt-11 mRNA levels compared with matched adjacent tissues. Expression was significantly upregulated during PDAC progression (TNM stage I to II) and maintained (TNM stages III and IV). Wnt-11 is expressed in PDAC in vitro and in vivo and plays a significant role in the pathophysiology of the disease; this evidence leads to the conclusion that Wnt-11 could serve as a novel, functional biomarker PDAC.
View Full-Text
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Dart, D.A.; Arisan, D.E.; Owen, S.; Hao, C.; Jiang, W.G.; Uysal-Onganer, P. Wnt-11 Expression Promotes Invasiveness and Correlates with Survival in Human Pancreatic Ductal Adeno Carcinoma. Genes 2019, 10, 921.
Show more citation formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
- Supplementary File 1:
XLSX-Document (XLSX, 1027 KB)
- Supplementary File 2:
ZIP-Document (ZIP, 927 KB)
