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Oncogenic B-Raf abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells |
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| Authors: | Ling Zhang Ruyi Shi Chanting He Caixia Cheng Bin Song Heyang Cui Yanyan Zhang Zhiping Zhao Yanghui Bi Xiaofeng Yang Xiaoping Miao Jiansheng Guo Xing Chen Jinfen Wang Yaoping Li Xiaolong Cheng Jing Liu Yongping Cui |
| Affiliation: | 1. Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;2. Department of Cell Biology & Genetics, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;3. Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;4. Department of Pathology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;5. Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;6. Department of General Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;g Department of Urology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;h Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, PR China;i Department of Endoscopy, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi 030001, PR China;j Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001, PR China |
| Abstract: | Activating B-Raf mutations that deregulate the mitogen-activated protein kinase (MAPK) pathway commonly occur in cancer. Although B-RafV600E induces increased Mps1 protein contributing to centrosome amplification and chromosome instability, the regulatory mechanisms of Mps1 in melanoma cells is not fully understood. Here, we report that Mps1/AKT and B-RafWT/ERK signaling form an auto-regulatory negative feedback loop in melanoma cells; notably, oncogenic B-RafV600E abrogates the negative feedback loop, contributing the aberrant Mps1 functions and tumorigenesis. Our findings raise the possibility that targeting the oncogenic B-Raf and Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment. |
| Keywords: | Mps1 AKT B-Raf/ERK signaling Negative feedback B-RafV600E Melanoma |
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