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Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.
|Title||Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Zhang L, Shi R, He C, Cheng C, Song B, Cui H, Zhang Y, Zhao Z, Bi Y, Yang X, Miao X, Guo J, Chen X, Wang J, Li Y, Cheng X, Liu J, Cui Y|
|Date Published||2013 Aug 28|
Activating B-Raf mutations that deregulate the mitogen-activated protein kinase (MAPK) pathway commonly occur in cancer. Although B-Raf(V600E) 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-Raf(WT)/ERK signaling form an auto-regulatory negative feedback loop in melanoma cells; notably, oncogenic B-Raf(V600E) 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.
|Alternate Journal||Cancer Lett.|