Association of nuclear-localized Nemo-like kinase with heat-shock protein 27 inhibits apoptosis in human breast cancer cells

PLoS One. 2014 May 9;9(5):e96506. doi: 10.1371/journal.pone.0096506. eCollection 2014.

Abstract

Nemo-like kinase (NLK), a proline-directed serine/threonine kinase regulated by phosphorylation, can be localized in the cytosol or in the nucleus. Whether the localization of NLK can affect cell survival or cell apoptosis is yet to be disclosed. In the present study we found that NLK was mainly localized in the nuclei of breast cancer cells, in contrast to a cytosolic localization in non-cancerous breast epithelial cells. The nuclear localization of NLK was mediated through direct interaction with Heat shock protein 27 (HSP27) which further protected cancer cells from apoptosis. The present study provides evidence of a novel mechanism by which HSP27 recognizes NLK in the breast cancer cells and prevents NLK-mediated cell apoptosis.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism
  • Down-Regulation
  • Etoposide / pharmacology
  • Female
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MCF-7 Cells
  • Microscopy, Confocal
  • Molecular Chaperones
  • Mutation
  • Phosphorylation
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Tumor Necrosis Factor-alpha
  • Etoposide
  • NLK protein, human
  • Protein Serine-Threonine Kinases

Grants and funding

The study was supported by the Swedish Cancer Foundation, the Swedish Medical Research Council, the Gunnar Nilsson Foundation, the Gyllenstiernska Kapperups Foundation, the BioCARE program, the Magnus Bergvall Foundation, the Royal Physiographic Society in Lund, and by funding from the European Research Council (ERC), under the European Union's Seventh Framework Programme for Research and Technology Development, grant agreement no. [260460], awarded to RM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.