Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice.
ApcMin/+ mice are regarded as a standard animal model of colorectal cancer (CRC). Tensin4 (TNS4 or Cten) is a putative oncogene conferring features of stemness and promoting motility. Our objective was to assess TNS4 expression in intestinal adenomas and determine whether TNS4 is upregulated by Wnt signalling. ApcMin/+ mice (n = 11) were sacrificed at approximately 120 days old at the onset of anaemia signs. Small intestines were harvested, and Swiss roll preparations were tested for TNS4 expression by immunohistochemistry (IHC). Individual polyps were also separately collected (n = 14) and tested for TNS4 mRNA expression and Kras mutation. The relationship between Wnt signalling and TNS4 expression was tested by Western blotting in the human CRC cell line HCT116 after inhibition of β-catenin activity with MSAB or its increase by transfection with a Flag β-catenin expression vector. Overall, 135/148 (91.2%) of the total intestinal polyps were positive for TNS4 expression by IHC, whilst adjacent normal areas were negative. RT-qPCR analysis showed approximately 5-fold upregulation of TNS4 mRNA in the polyps compared to adjacent normal tissue and no Kras mutations were detected. In HCT116, β-catenin inhibition resulted in reduced TNS4 expression, and conversely, β-catenin overexpression resulted in increased TNS4 expression. In conclusion, this is the first report linking aberrant Wnt signalling to upregulation of TNS4 both during initiation of intestinal adenomas in mice and in in vitro models. The exact contribution of TNS4 to adenoma development remains to be investigated, but the ApcMin/+ mouse represents a good model to study this.
['Raposo|Teresa P|TP|0000-0003-4033-8498', 'Alfahed|Abdulaziz|A|', 'Nateri|Abdolrahman S|AS|', 'Ilyas|Mohammad|M|']
D018256:Adenomatous Polyps D000818:Animals D004195:Disease Models, Animal D005260:Female D015972:Gene Expression Regulation, Neoplastic D017491:Genes, APC D045325:HCT116 Cells D006801:Humans D007414:Intestinal Neoplasms D007421:Intestine, Small D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D000070876:Tensins D015854:Up-Regulation D060449:Wnt Signaling Pathway D051176:beta Catenin
TNS4 Wnt signalling multiple intestinal neoplasia HCT116 Apc
Min/+