Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice

Raposo, Teresa P.; Alfahed, Abdulaziz; Nateri, Abdolrahman S.; Ilyas, Mohammad

Abstract

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 120days 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.

Citation

Raposo, T. P., Alfahed, A., Nateri, A. S., & Ilyas, M. (2020). Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice. International Journal of Experimental Pathology, 101(3-4), 80-86. https://doi.org/10.1111/iep.12352

• Journal Article Type: Article
• Acceptance Date: May 12, 2020
• Online Publication Date: Jun 22, 2020
• Publication Date: 2020-06
• Deposit Date: Nov 24, 2022
• Publicly Available Date: Nov 29, 2022
• Journal: International Journal of Experimental Pathology
• Print ISSN: 0959-9673
• Electronic ISSN: 1365-2613
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 101
• Issue: 3-4
• Pages: 80-86
• DOI: https://doi.org/10.1111/iep.12352
• Keywords: Pathology and Forensic Medicine; Cell Biology; Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/4795940
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/iep.12352