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Clinical & Experimental Metastasis

, Volume 32, Issue 8, pp 755–767 | Cite as

Enrichment of nuclear S100A4 during G2/M in colorectal cancer cells: possible association with cyclin B1 and centrosomes

  • Eivind Valen Egeland
  • Kjetil Boye
  • Solveig J. Pettersen
  • Mads H. Haugen
  • Tove Øyjord
  • Lene Malerød
  • Kjersti Flatmark
  • Gunhild M. Mælandsmo
Research Paper

Abstract

S100A4 promotes metastasis in several types of cancer, but the involved molecular mechanisms are still incompletely described. The protein is associated with a wide variety of biological functions and it locates to different subcellular compartments, including nuclei, cytoplasm and extracellular space. Nuclear expression of S100A4 has been associated with more advanced disease stage as well as poor outcome in colorectal cancer (CRC). The present study was initiated to investigate the nuclear function of S100A4 and thereby unravel potential biological mechanisms linking nuclear expression to a more aggressive phenotype. CRC cell lines show heterogeneity in nuclear S100A4 expression and preliminary experiments revealed cells in G2/M to have increased nuclear accumulation compared to G1 and S cells, respectively. Synchronization experiments validated nuclear S100A4 expression to be most prominent in the G2/M phase, but manipulating nuclear levels of S100A4 using lentiviral modified cells failed to induce changes in cell cycle distribution and proliferation. Proximity ligation assay did, however, demonstrate proximity between S100A4 and cyclin B1 in vitro, while confocal microscopy showed S100A4 to localize to areas corresponding to centrosomes in mitotic cells prior to chromosome segregation. This might indicate a novel and uncharacterized function of the metastasis-associated protein in CRC cells.

Keywords

Colorectal cancer S100A4 Nucleus Cell cycle Cyclin B1 Centrosomes 

Notes

Acknowledgments

We would like to thank Stein Waagene for carrying out the animal experiments and Dr. Vivi Ann Flørenes for valuable feedback and discussion. The present work was kindly supported by the Norwegian Cancer Society (Grant No [#4218523581] to EVE).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10585_2015_9742_MOESM1_ESM.pdf (600 kb)
Supplementary material 1 (PDF 599 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Eivind Valen Egeland
    • 1
  • Kjetil Boye
    • 1
    • 3
  • Solveig J. Pettersen
    • 1
  • Mads H. Haugen
    • 1
  • Tove Øyjord
    • 1
  • Lene Malerød
    • 2
  • Kjersti Flatmark
    • 1
    • 4
    • 5
  • Gunhild M. Mælandsmo
    • 1
    • 6
  1. 1.Department of Tumor Biology, Institute for Cancer ResearchThe Norwegian Radium Hospital, Oslo University HospitalOsloNorway
  2. 2.Department of Molecular Cell Biology, Institute for Cancer ResearchThe Norwegian Radium Hospital, Oslo University HospitalOsloNorway
  3. 3.Department of OncologyThe Norwegian Radium Hospital, Oslo University HospitalOsloNorway
  4. 4.Department of Gastroenterological SurgeryThe Norwegian Radium Hospital, Oslo University HospitalOsloNorway
  5. 5.Institute of Clinical MedicineUniversity of OsloOsloNorway
  6. 6.Department of PharmacyUniversity of TromsøTromsøNorway

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