REGγ accelerates melanoma formation by regulating Wnt/β-catenin signalling pathway
| Autor: | Lei Li, Liangfang Yao, Bhatti Muhammad Zeeshan, Yongyan Dang, Tenghui Chen, Tingmei Huang, Di Zuo, Abdus Saboor Shah, Linian Pan, Tielong Liu, Qingwei Wang, Geng Chen, Zhengwang Sun, Jiwei Chen, Kun Li, Jian Liu, Lu Tong, Ke Li, Chan Jiao, Kewen Hu, Hui Chen, Xiao Gao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Cell Dermatology Biochemistry Autoantigens 03 medical and health sciences Mice Cell Line Tumor medicine Animals Humans RNA Messenger RNA Small Interfering neoplasms Molecular Biology Melanoma Wnt Signaling Pathway beta Catenin Cell Proliferation Gene knockdown Glycogen Synthase Kinase 3 beta Activator (genetics) Cell growth Chemistry Wnt signaling pathway medicine.disease G1 Phase Cell Cycle Checkpoints In vitro 030104 developmental biology medicine.anatomical_structure Proteasome Gene Knockdown Techniques Cancer research Female Neoplasm Transplantation |
| Zdroj: | Experimental dermatology. 26(11) |
| ISSN: | 1600-0625 |
| Popis: | It has been reported that the proteasome activator REGγ is associated with multiple oncogenic pathways in human cancers. However, the role of REGγ in the development of melanoma and the underlying mechanisms remain unclear. In this study, we attempted to investigate the effects of REGγ on human melanoma cell proliferation in vitro and in vivo. We demonstrated that knockdown of REGγ inhibited melanoma cell growth and arrested melanoma cell at G1 phase. Furthermore, depletion of REGγ also inhibited the xenograft growth of human melanoma. Mechanistically, REGγ activates Wnt/β-catenin signal pathway by degrading GSK-3β in melanoma cell lines and mouse models. Transient knockdown of β-catenin effectively blocked cell proliferation in REGγ wild-type melanoma cells. In human melanoma samples, REGγ was overexpressed and positively correlated with β-catenin levels. This study demonstrates that REGγ is a central molecule in the development of melanoma by regulating Wnt/β-catenin pathway. This suggests that targeting REGγ could be an alternative therapeutic approach for melanoma. |
| Databáze: | OpenAIRE |
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