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

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• 作者：Mikayo Aragaki ; Kiichiro Tsuchiya ; Ryuichi Okamoto ; Sanae Yoshioka ; Tetsuya Nakamura ; Naoya Sakamoto ; Takanori Kanai ; Mamoru Watanabe
• 关键词：Atoh1 ; Hath1 ; Proteasomal degradation ; Differentiation ; Wnt ; GSK3β ; Colon cancer
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：18 April 2008
• 年：2008
• 卷：368
• 期：4
• 页码：923-929
• 全文大小：367 K

文摘

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.