Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling
| Autor: | Qin-Qin Liu, Xiao-Shan Zhu, Ya-Li Zhao, Jun-Tang Li, Hongxia Liu, Chun-Fang Gao, Xusheng Zhao, Ning-Ning Liu, Changsong Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Aging proliferation FOXO1 Apoptosis Mice SCID Metastasis Proto-Oncogene Proteins c-myc Mice Western blot Sirtuin 1 Cell Movement Stomach Neoplasms Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Nicotinamide Phosphoribosyltransferase Adaptor Proteins Signal Transducing Aged Cell Proliferation Gene knockdown medicine.diagnostic_test Chemistry Forkhead Box Protein O1 gastric cancer Cancer YAP-Signaling Proteins Cell Biology Middle Aged medicine.disease invasion Prognosis Cell culture Gene Knockdown Techniques ubiquitin-specific peptidase 22 Cancer research Cytokines Female Signal transduction Ubiquitin Thiolesterase Research Paper Signal Transduction Transcription Factors |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | In this study, we investigated the role of ubiquitin-specific protease 22 (USP22) in the growth and progression of gastric cancer (GC). USP22 mRNA and protein levels were significantly higher in GC tissue samples and GC cell lines than in adjacent noncancerous tissue samples and a normal gastric mucosal epithelial cell line (GES1), respectively. USP22 knockdown significantly decreased in vitro survival, proliferation, migration, and invasiveness of GC cells compared with the controls. Western blot analysis of control and USP22-silenced GC cells showed that USP22 modulates the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways. Subcutanenous injection of USP22-silenced GC cells into SCID mice generated significantly smaller xenograft tumors than did control cells. Moreover, USP22-silenced GC cells showed less lung metastasis than the controls following tail vein injection in SCID mice. In addition, high USP22 expression correlated positively with tumor size, advanced stage and metastasis, and correlated negatively with tumor differentiation and prognosis in GC patients. These results show that USP22 regulates growth and progression of GC via the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways. |
| Databáze: | OpenAIRE |
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