Author/Authors :
Zhang، نويسنده , , Ling and Shi، نويسنده , , Ruyi and He، نويسنده , , Chanting and Cheng، نويسنده , , Caixia and Song، نويسنده , , Song-Bin and Cui، نويسنده , , Heyang and Zhang، نويسنده , , Yanyan and Zhao، نويسنده , , Zhiping and Bi، نويسنده , , Yanghui and Yang، نويسنده , , Xiaofeng and Miao، نويسنده , , Xiaoping and Guo، نويسنده , , Jiansheng and Chen، نويسنده , , Xing and Wang، نويسنده , , Jinfen and Li، نويسنده , , Yaoping and Cheng، نويسنده , , Xiaolong and Liu، نويسنده , , Jing and Cui، نويسنده , , Yongping، نويسنده ,
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 :
Negative feedback , B-Raf/ERK signaling , Akt , Mps1 , melanoma , B-RafV600E
