Proteasomal degradation of Atoh1 by aberrant Wnt signaling maintains the undifferentiated state of colon cancer

被引：34

作者：

Aragaki, Mikayo ^{[1
]}

Tsuchiya, Kiichiro ^{[1
]}

Okamoto, Ryuichi ^{[1
]}

Yoshioka, Sanae ^{[1
]}

Nakamura, Tetsuya ^{[1
]}

Sakamoto, Naoya ^{[1
]}

Kanai, Takanorl ^{[1
]}

Watanabe, Mamoru ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch, Dept Gastroenterol & Hepatol, Bunkyo Ku, Tokyo 1138519, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 368卷 / 04期

关键词：

Atoh1; Hath1; proteasomal degradation; differentiation; Wnt; GSK3; beta; colon cancer;

D O I：

10.1016/j.bbrc.2008.02.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Atoh1 plays a crucial role in intestinal cell differentiation. We have demonstrated that its human homolog Hath1 protein is targeted by the Wnt-GSK3 axis, resulting in the proteasomal degradation in human colon cancer. However, the contribution of Hath1 degradation to the undifferentiated state of colon cancer remains unknown. In this study, we demonstrated that both constitutive expression of mutant Hath1 and stabilization of Hath1 protein by a GSK3 inhibitor in colon cancer cells increased the expression of MUC2 known as a representative function of differentiated goblet cells. This means that Hath1 protein degradation may be required for maintaining the undifferentiated state of colon cancers, and that GSK3 inhibitors have potential for use in cancer therapy. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：923 / 929

页数：7

共 24 条

[1] A MAMMALIAN HELIX-LOOP-HELIX FACTOR STRUCTURALLY RELATED TO THE PRODUCT OF DROSOPHILA PRONEURAL GENE ATONAL IS A POSITIVE TRANSCRIPTIONAL REGULATOR EXPRESSED IN THE DEVELOPING NERVOUS-SYSTEM [J].