Wnt-11 Expression Promotes Invasiveness and Correlates with Survival in Human Pancreatic Ductal Adeno Carcinoma

Dafydd A Dart, Damla E Arisan, Sioned Owen, Chunyi Hao, Wen G Jiang, Pinar Uysal-Onganer

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Abstract

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.

Original languageEnglish
JournalGenes
Volume10
Issue number11
DOIs
Publication statusPublished - 11 Nov 2019

Keywords

  • Biomarkers, Tumor/genetics
  • Biopsy
  • Carcinoma, Pancreatic Ductal/genetics
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial-Mesenchymal Transition/genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness/genetics
  • Neoplasm Staging
  • Pancreas/pathology
  • Pancreatic Neoplasms/genetics
  • RNA, Small Interfering/metabolism
  • RNA-Seq
  • Survival Analysis
  • Up-Regulation
  • Wnt Proteins/genetics

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