Localization of MCT2 at peroxisomes is associated with malignant transformation in prostate cancer

J Cell Mol Med. 2015 Apr;19(4):723-33. doi: 10.1111/jcmm.12481. Epub 2015 Jan 30.

Abstract

Previous studies on monocarboxylate transporters expression in prostate cancer (PCa) have shown that monocarboxylate transporter 2 (MCT2) was clearly overexpressed in prostate malignant glands, pointing it out as a putative biomarker for PCa. However, its localization and possible role in PCa cells remained unclear. In this study, we demonstrate that MCT2 localizes mainly at peroxisomes in PCa cells and is able to take advantage of the peroxisomal transport machinery by interacting with Pex19. We have also shown an increase in MCT2 expression from non-malignant to malignant cells that was directly correlated with its peroxisomal localization. Upon analysis of the expression of several peroxisomal β-oxidation proteins in PIN lesions and PCa cells from a large variety of human prostate samples, we suggest that MCT2 presence at peroxisomes is related to an increase in β -oxidation levels which may be crucial for malignant transformation. Our results present novel evidence that may not only contribute to the study of PCa development mechanisms but also pinpoint novel targets for cancer therapy.

Keywords: MCT2; peroxisomes; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basigin / metabolism
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic / metabolism*
  • Cytoplasm / metabolism
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Monocarboxylic Acid Transporters / metabolism*
  • Oxidation-Reduction
  • Peroxisomes / metabolism*
  • Prostate / cytology
  • Prostate / metabolism
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • Protein Isoforms / metabolism
  • Repressor Proteins / metabolism

Substances

  • BSG protein, human
  • Membrane Proteins
  • Monocarboxylic Acid Transporters
  • PEX14 protein, human
  • Protein Isoforms
  • Repressor Proteins
  • SLC16A7 protein, human
  • Basigin
  • PEX19 protein, human