title: Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.
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.
authors.affiliation: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Ruyi
authors.initials: R
authors.lastname: Shi
authors.forename: Chanting
authors.initials: C
authors.lastname: He
authors.forename: Caixia
authors.initials: C
authors.lastname: Cheng
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Heyang
authors.initials: H
authors.lastname: Cui
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Bi
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Guo
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.forename: Jinfen
authors.initials: J
authors.lastname: Wang
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cui
mesh_terms: D018797:Cell Cycle Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D025461:Feedback, Physiological; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D011505:Protein-Tyrosine Kinases; C482119:BRAF protein, human; D017346:Protein Serine-Threonine Kinases; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; C075840:TTK protein, human
keywords: AKT; B-Raf(V600E); B-Raf/ERK signaling; Melanoma; Mps1; Negative feedback