Translational and Regulatory Sciences
Online ISSN : 2434-4974
Oncology
Suppression of tensin 2 promotes intestinal tumorigenesis by liberating integrin-linked kinase-induced nuclear translocation of β-catenin
Koki HIURAAya SAKANOUESosuke KONTANIYuki TAKAHASHIMasaki WATANABEKenta NAKANOTadashi OKAMURARyo ANDOShigeru KAKUTAHayato SASAKINobuya SASAKI
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2020 Volume 2 Issue 2 Pages 51-59

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Abstract

Tensin 2 (TNS2) is a focal adhesion-localized multidomain protein expressed in various tissues. TNS2 expression significantly decreases in many tumor cell lines, and low TNS2 expression is associated with a poorer relapse-free survival in some cancers, suggesting that the loss of TNS2 may be related to tumor progression. Deregulation of Wnt/β-catenin signaling is frequently observed in colorectal cancer. In the present study, we found that TNS2 negatively regulated Wnt signaling by suppressing the nuclear translocation of β-catenin by reducing integrin-linked kinase (ILK) activity in colon cancer cell lines. To investigate the role of TNS2 in intestinal tumorigenesis in vivo, we introduced Tns2 mutation into ApcMin/+ mouse, a model of human familial adenomatous polyposis. The compound mutant mice showed a significant increase in tumor number and size in the small intestine and colon. Thus, this study may contribute to the discovery of novel mechanisms underlying cancer malignancy, and pave the way for the development of treatment strategies for intestinal cancers.

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© 2020 Catalyst Unit

This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license.
https://creativecommons.org/licenses/by-nc-nd/4.0/
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