The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways
| العنوان: | The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways |
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| المؤلفون: | Shengkai Huang, Qing Luo, Mei Zhao, Zhao-xu Zheng, Lin Yang, Ping Liu, Xinghua Yuan, Jia Wang, Hua Peng, Changzhi Huang, Yu-yu Gu, Mei Yang |
| المصدر: | Tumor Biology. 36:8379-8387 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Pathology, medicine.medical_specialty, MAP Kinase Signaling System, Biology, Metastasis, Western blot, Cell Movement, Stomach Neoplasms, Cell Line, Tumor, medicine, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Protein kinase B, Cell Proliferation, medicine.diagnostic_test, Cell growth, Liver Neoplasms, Cancer, Cell migration, General Medicine, medicine.disease, Gene Expression Regulation, Neoplastic, Oncogene Protein v-akt, Cell culture, Cancer research, Immunohistochemistry, Female, Ubiquitin Thiolesterase, Signal Transduction |
| الوصف: | 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. |
| تدمد: | 1423-0380 1010-4283 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91ee234b91ac1238206a3b4f7eb6b537Test https://doi.org/10.1007/s13277-015-3566-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....91ee234b91ac1238206a3b4f7eb6b537 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14230380 10104283 |
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