Suppression of tensin 2 promotes intestinal tumorigenesis by liberating integrin-linked kinase-induced nuclear translocation of β-catenin

Koki HIURA, Aya SAKANOUE, Sosuke KONTANI, Yuki TAKAHASHI, Masaki WATANABE, Kenta NAKANO, Tadashi OKAMURA, Ryo ANDO, Shigeru KAKUTA, Hayato SASAKI, Nobuya SASAKI
2020 Translational and Regulatory Sciences  
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
more » ... ing 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 Apc Min/+ 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. Key words: Tensin 2, tumor suppressor, adenomatous polyposis coli, Wnt/β-catenin pathway, integrin-linked kinase Highlights 1. Knockdown or overexpression of TNS2 in colon cancer cell lines increases or decreases their proliferation and migration, respectively. 2. TNS2 inhibits Wnt signaling by suppressing β-catenin nuclear translocation via reduction in ILK activity. 3. Genetic disruption of Tns2 on the Apc-deficient background results in a significant increase in tumor number and size in the intestine.
doi:10.33611/trs.2020-009 fatcat:iaijaf2ulbau7awv5l6gy3vslm