Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.

TitleOncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsZhang 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
JournalCancer letters
Volume337
Issue1
Pagination125-32
Date Published2013 Aug 28
Abstract

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.

DOI10.1155/2013/748435
Alternate JournalCancer Lett.