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

Cancer Lett. 2013 Aug 28;337(1):125-32. doi: 10.1016/j.canlet.2013.05.029. Epub 2013 May 29.


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.

Keywords: AKT; B-Raf(V600E); B-Raf/ERK signaling; Melanoma; Mps1; Negative feedback.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / physiology*
  • Cell Line, Tumor
  • Feedback, Physiological
  • Humans
  • MAP Kinase Signaling System
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mutation*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / physiology*
  • Protein-Tyrosine Kinases / physiology*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / physiology
  • Proto-Oncogene Proteins c-akt / physiology*


  • Cell Cycle Proteins
  • Protein-Tyrosine Kinases
  • BRAF protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-akt
  • TTK protein, human