UCHL1 acts as a colorectal cancer oncogene via activation of the β-catenin/TCF pathway through its deubiquitinating activity

Zhong,Jialing; Zhao,Mei; Ma,Yiming; Luo,Qing; Liu,Jian; Wang,Jia; Yuan,Xinghua; Sang,Jianli; Huang,Changzhi

doi:10.3892/ijmm.2012.1012

August 2012 Volume 30 Issue 2

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August 2012 Volume 30 Issue 2

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Article

UCHL1 acts as a colorectal cancer oncogene via activation of the β-catenin/TCF pathway through its deubiquitinating activity

Authors:
- Jialing Zhong
- Mei Zhao
- Yiming Ma
- Qing Luo
- Jian Liu
- Jia Wang
- Xinghua Yuan
- Jianli Sang
- Changzhi Huang
View Affiliations / Copyright

Affiliations: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Department of Abdomen Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, P.R. China
Pages: 430-436
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Published online on: May 25, 2012

https://doi.org/10.3892/ijmm.2012.1012
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Abstract

Ubiquitin C-terminal hydrolase-L1 (UCHL1) belongs to the family of deubiquitinating enzymes (DUBs), which is involved in the ubiquitin-dependent proteolytic system. Previously, we have reported that the upregulation of UCHL1 is related to lymph node metastasis in colorectal cancer (CRC). However, its molecular mechanisms remain elusive. In this study, we transfected pcDNA3.1/UCHL1 and the pcDNA3.1/UCHL1-C90S mutant into HCT8 cells. The changes in biological features in these stable transfectants were examined both in vitro and in vivo. Western blot analysis was used to analyze the changes in the β-catenin/T cell factor (TCF) pathway. We demonstrated that UCHL1 re-expression promoted the proliferation, migration and metastasis potential of HCT8 cells both in vitro and in vivo. We also found that UCHL1 could decelerate β-catenin degradation depending on its deubiquitinating activity. The accumulated β-catenin consequently activated the β-catenin/TCF pathway and induced the expression of cyclin D1 and uPA. These observations imply that UCHL1 may contribute to CRC progression by activating the β-catenin/TCF pathway through its deubiquitinating activity.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

UCHL1 acts as a colorectal cancer oncogene via activation of the β-catenin/TCF pathway through its deubiquitinating activity

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