Usp7 promotes medulloblastoma cell survival and metastasis by activating Shh pathway
| Autor: | Xu He, Mei-Xiao Zhan, Zizhang Zhou, Ligong Lu, Jinxiao Liu, Yan Li, Yong Li, Xiaohan Sun |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Biophysics medicine.disease_cause Biochemistry Metastasis Ubiquitin-Specific Peptidase 7 03 medical and health sciences Cell Movement Cell Line Tumor medicine Humans PTEN Hedgehog Proteins Viability assay Neoplasm Metastasis Molecular Biology Cell Proliferation Medulloblastoma Gene knockdown Base Sequence biology Cell growth Cell Biology medicine.disease 030104 developmental biology Cell culture Gene Knockdown Techniques biology.protein Cancer research Carcinogenesis Ubiquitin Thiolesterase |
| Zdroj: | Biochemical and Biophysical Research Communications. 484:429-434 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2017.01.144 |
| Popis: | The ubiquitin-specific protease Usp7 plays roles in multiple cellular processes through deubiquitinating and stabilizing numerous substrates, including P53, Pten and Gli. Aberrant Usp7 activity has been implicated in many disorders and tumorigenesis, making it as a potential target for therapeutic intervention. Although it is clear that Usp7 is involved in many types of cancer, its role in regulating medulloblastoma (MB) is still unknown. In this study, we show that knockdown of Usp7 inhibits the proliferation and migration of MB cells, while Usp7 overexpression exerts an opposite effect. Furthermore, we establish Usp7 knockout MB cell line using the CRISPR/Cas9 system and further confirm that Usp7 knockout also blocks MB cell proliferation and metastasis. In addition, we reveal that knockdown of Usp7 compromises Shh pathway activity and decrease Gli protein levels, while P53 level and P53 target gene expression have no obvious changes. Finally, we find that Usp7 inhibitors apparently inhibit MB cell viability and migration. Taken together, our findings suggest that Usp7 is important for MB cell proliferation and metastasis by activating Shh pathway, and is a putative therapeutic target for MBs. |
| Databáze: | OpenAIRE |
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