Roles of Copper-Binding Proteins in Breast Cancer

Int J Mol Sci. 2017 Apr 20;18(4):871. doi: 10.3390/ijms18040871.

Abstract

Copper ions are needed in several steps of cancer progression. However, the underlying mechanisms, and involved copper-binding proteins, are mainly elusive. Since most copper ions in the body (in and outside cells) are protein-bound, it is important to investigate what copper-binding proteins participate and, for these, how they are loaded with copper by copper transport proteins. Mechanistic information for how some copper-binding proteins, such as extracellular lysyl oxidase (LOX), play roles in cancer have been elucidated but there is still much to learn from a biophysical molecular viewpoint. Here we provide a summary of copper-binding proteins and discuss ones reported to have roles in cancer. We specifically focus on how copper-binding proteins such as mediator of cell motility 1 (MEMO1), LOX, LOX-like proteins, and secreted protein acidic and rich in cysteine (SPARC) modulate breast cancer from molecular and clinical aspects. Because of the importance of copper for invasion/migration processes, which are key components of cancer metastasis, further insights into the actions of copper-binding proteins may provide new targets to combat cancer.

Keywords: ATOX1; MEMO1; SPARC; breast cancer; cancer; copper transport; copper-binding protein; lysyl oxidase; metastasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Copper / metabolism*
  • Copper Transport Proteins
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Metallochaperones / metabolism
  • Models, Biological
  • Molecular Chaperones
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Osteonectin / metabolism
  • Oxidation-Reduction
  • Protein-Lysine 6-Oxidase / metabolism

Substances

  • ATOX1 protein, human
  • Carrier Proteins
  • Copper Transport Proteins
  • Metallochaperones
  • Molecular Chaperones
  • Osteonectin
  • copper-binding protein
  • Copper
  • Protein-Lysine 6-Oxidase