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Published on: September 30, 2016
TLE4 promotes colorectal cancer progression through activation of JNK/c-Jun signaling pathway
Shu-Yang Wang1,2,3, Ke Gao1,2,3,4, Dan-Ling Deng1,2,3
1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Abstract:
The Groucho transcriptional co-repressor TLE4 protein has been shown to be a tumor suppressor in a subset of acute myeloid leukemia. However, little is known about its role in development and progression of solid tumor. In this study, we found that the expression of TLE4 in colorectal cancer (CRC) tissues was significantly higher than that in their matched adjacent intestine epithelial tissues. In addition, high expression of TLE4 was significantly correlated with advanced Dukes stage, lymph node metastasis and poor prognosis of CRC. Moreover, enforced expression of TLE4 in CRC cell lines significantly enhanced proliferation, invasion and tumor growth. On the contrary, knock down of TLE4 repressed cell proliferation, invasion and tumor growth. Furthermore, our study exhibited that the TLE4 promoted cell proliferation and invasion partially via activation of JNK-c-Jun pathway and subsequently increased cyclinD1 and decreased P27Kip1 expression. In conclusion, these results suggested that TLE4, a potential prognostic biomarker for CRC, plays an important role in the development and progression of human CRC.
Insights
The TLE4 protein promotes colorectal cancer (CRC) growth and spread, contrary to its tumor suppressor role in leukemia. High TLE4 expression correlates with advanced CRC, indicating its potential as a prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The transcriptional co-repressor TLE4 is a known tumor suppressor in acute myeloid leukemia.
- Its role in solid tumor development and progression, particularly colorectal cancer (CRC), remains largely unknown.
Purpose of the Study:
- To investigate the role of TLE4 in the development and progression of colorectal cancer.
- To determine TLE4's potential as a prognostic biomarker in CRC.
Main Methods:
- Quantitative analysis of TLE4 expression in CRC tissues versus adjacent normal tissues.
- Correlation analysis between TLE4 expression levels and clinical parameters (Dukes stage, lymph node metastasis, prognosis).
- In vitro and in vivo studies involving TLE4 overexpression and knockdown in CRC cell lines.
- Investigation of the molecular pathways affected by TLE4, including the JNK-c-Jun pathway, cyclinD1, and P27Kip1.
Main Results:
- TLE4 expression is significantly elevated in CRC tissues compared to normal adjacent tissues.
- High TLE4 expression is associated with advanced Dukes stage, lymph node metastasis, and poorer patient prognosis.
- Enforced TLE4 expression enhances CRC cell proliferation, invasion, and tumor growth, while TLE4 knockdown inhibits these processes.
- TLE4 promotes CRC progression partly by activating the JNK-c-Jun pathway, leading to increased cyclinD1 and decreased P27Kip1 levels.
Conclusions:
- TLE4 plays a significant role in the development and progression of human colorectal cancer.
- TLE4 is a potential prognostic biomarker for CRC, with elevated expression indicating a worse outcome.
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