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The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways

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Tumor Biology

Abstract

Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a de-ubiquitinating enzyme, which enzymatic activity relies on the C90 site. The function of UCHL1 is controversial in different types of cancer, and its role in gastric cancer progression remains unclear. In this study, immunohistochemistry staining was applied to detect the expression of UCHL1 in primary gastric cancer and liver metastases from gastric cancer. MKN45 and BGC823 cell lines with stable expression of de-ubiquitinase active UCHL1 or inactive UCHL1-variant C90S were established by lentiviral infection. The effect of UCHL1 on cell proliferation was evaluated by MTT and colony formation assays. The abilities of cell migration and invasion were determined by transwell assay. Protein expression levels were determined by Western blot. The results indicated that UCHL1 had a significantly higher positive expression rate in liver metastases from gastric cancer compared with primary gastric cancer. Overexpression of UCHL1 in MKN45 and BGC823 cells promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity. UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion. These findings demonstrated that UCHL1 promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity by activating Akt and Erk1/2, which may account for its higher positive expression rate in liver metastases from gastric cancer. UCHL1 could be a candidate biomarker and a therapeutic target for gastric cancer metastasis.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81472208) and the Open Projects of State Key Laboratory of Molecular Oncology (SKL-KF-2015-12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. 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, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China

    Yu-yu Gu, Mei Yang, Mei Zhao, Hua Peng, Jia Wang, Sheng-kai Huang & Chang-zhi Huang

  2. Affiliated Hospital of Zunyi Medical College, Zunyi, 563003, China

    Qing Luo

  3. Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China

    Lin Yang

  4. Department of Abdomen Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China

    Zhao-xu Zheng & Xing-hua Yuan

  5. The Institute of Clinical Pharmacology of Chinese PLA General Hospital, Beijing, China

    Ping Liu

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  1. Yu-yu Gu
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  2. Mei Yang
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  3. Mei Zhao
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  5. Lin Yang
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  9. Zhao-xu Zheng
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  10. Xing-hua Yuan
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Correspondence to Zhao-xu Zheng, Xing-hua Yuan, Ping Liu or Chang-zhi Huang.

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Gu, Yy., Yang, M., Zhao, M. et al. The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways. Tumor Biol. 36, 8379–8387 (2015). https://doi.org/10.1007/s13277-015-3566-0

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  • DOI: https://doi.org/10.1007/s13277-015-3566-0

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