Translocation of BBAP from the cytoplasm to the nucleus reduces the metastatic ability of vemurafenib-resistant SKMEL28 cells

Mol Med Rep. 2017 Jan;15(1):317-322. doi: 10.3892/mmr.2016.5976. Epub 2016 Dec 2.

Abstract

To the best of our knowledge, the present study is the first to demonstrate that treatment of vemurafenib-resistant SKMEL28 (SKMEL28-R) cells with paclitaxel leads to a shift in localization of the E3-ligase BBAP from the cytoplasm to the nucleus, consequently decreasing the metastatic ability of this cell line. The present study revealed that the movement of BBAP from the cytoplasm to nucleus initiated a change in cell morphology. In addition, the translocation of BBAP led to a decrease of metastatic characteristics in SKMEL28‑R cells, including migration and invasion via downregulation of the phosphorylated form of focal adhesion kinase and N‑cadherin, as well as an upregulation of p21 and E-cadherin. The results of the present study suggested that BBAP may not only be a novel biomarker for melanoma, but also a novel therapeutic target for treatment of metastatic melanoma.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Drug Resistance, Neoplasm
  • Humans
  • Indoles / pharmacology*
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology
  • Neoplasm Metastasis / prevention & control*
  • Paclitaxel / pharmacology*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Sulfonamides / pharmacology*
  • Ubiquitin-Protein Ligases / metabolism*
  • Vemurafenib

Substances

  • Antineoplastic Agents
  • Indoles
  • Sulfonamides
  • Vemurafenib
  • DTX3L protein, human
  • Ubiquitin-Protein Ligases
  • Paclitaxel