REGγ accelerates melanoma formation by regulating Wnt/β‐catenin signalling pathway |
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| Authors: | Hui Chen Xiao Gao Zhengwang Sun Qingwei Wang Di Zuo Linian Pan Kun Li Jiwei Chen Geng Chen Kewen Hu Ke Li Abdus Saboor Shah Tingmei Huang Bhatti Muhammad Zeeshan Lu Tong Chan Jiao Jian Liu Tenghui Chen Liangfang Yao Yongyan Dang Tielong Liu Lei Li |
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| Affiliation: | 1. Shanghai Key Laboratory of regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China;2. Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, China;3. Ningxia key laboratory of cerebrocranial diseases, Ningxia medical university, Ningxia Medical University, Yinchuan, China;4. Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA;5. Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA |
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| Abstract: | 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. |
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| Keywords: | GSK‐3β melanoma REGγ Wnt/β ‐catenin |
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