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Published on: June 17, 2014
TIPE1 impairs stemness maintenance in colorectal cancer through directly targeting β-catenin
Tao Ye1, Biwei Yang2, Chen Wang1
1Minhang Branch, Zhongshan Hospital, Fudan University; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
Abstract:
TIPE1 (tumor necrosis factor-α-induced protein 8-like 1) contributes to cell death in diverse cancers. However, the expression and biological functions of TIPE1 in colon cancer remain unclear. In the present study, we report that TIPE1 was downregulated in colon cancer tissues and positively correlates with prognosis of colon cancer patients. TIPE1 overexpression significantly inhibits colon cancer cell growth both in vitro and in vivo through impairing stemness, accompanied with downregulation of the stemness-related markers, ALDH, CD133, CD44 and SOX-9. Mechanically, TIPE1 directly targets β-catenin and promotes β-catenin degradation in a protease-dependent manner, and Wnt/β-catenin signaling plays a crucial role during TIPE1-mediated stemness inhibition in colon cancer. These findings reveal that TIPE1 exerts anti-tumor effects in colon cancer and suggest that TIPE1 would be a therapeutic target for cancers.
Insights
Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) is downregulated in colon cancer, inhibiting cancer cell growth by reducing stemness. TIPE1 targets β-catenin, suggesting its potential as a therapeutic target for colon cancer.
Area of Science:
- Oncology
- Molecular Biology
Background:
- TIPE1 (tumor necrosis factor-α-induced protein 8-like 1) is implicated in cancer cell death.
- The role of TIPE1 in colon cancer pathogenesis is not well understood.
Purpose of the Study:
- To investigate the expression and function of TIPE1 in colon cancer.
- To elucidate the mechanism underlying TIPE1's effect on colon cancer stemness and growth.
Main Methods:
- Analysis of TIPE1 expression in colon cancer tissues.
- In vitro and in vivo experiments assessing the impact of TIPE1 overexpression on colon cancer cell growth and stemness.
- Investigation of TIPE1's interaction with β-catenin and its effect on Wnt/β-catenin signaling.
Main Results:
- TIPE1 expression is downregulated in colon cancer tissues and correlates with poorer prognosis.
- Overexpression of TIPE1 inhibits colon cancer cell proliferation and stemness, reducing markers like ALDH, CD133, CD44, and SOX-9.
- TIPE1 directly targets and promotes the degradation of β-catenin, crucial for Wnt/β-catenin signaling inhibition.
Conclusions:
- TIPE1 exhibits anti-tumor effects in colon cancer by suppressing stemness via the Wnt/β-catenin pathway.
- TIPE1 represents a potential therapeutic target for colon cancer treatment.
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