KIFC1 is a novel potential therapeutic target for breast cancer

Cancer Biol Ther. 2015;16(9):1316-22. doi: 10.1080/15384047.2015.1070980. Epub 2015 Jul 15.

Abstract

Kinesin-like protein KIFC1, a normally nonessential kinesin motor, plays a critical role in centrosome clustering in cancer cells and is essential for the survival of cancer cells. Herein, we reported that KIFC1 expression is up-regulated in breast cancer, particularly in estrogen receptor negative, progesterone receptor negative and triple negative breast cancer, and is not associated with epidermal growth factor receptor 2 status. In addition, KIFC1 is highly expressed in all 8 tested human breast cancer cell lines, but is absent in normal human mammary epithelial cells and weakly expressed in 2 human lung fibroblast lines. Moreover, KIFC1 silencing significantly reduced breast cancer cell viability. Finally, we found that PJ34, a potent small molecule inhibitor of poly(ADP-ribose) polymerase, suppressed KIFC1 expression and induced multipolar spindle formation in breast cancer cells, and inhibited cell viability and colony formation within the same concentration range, suggesting that KIFC1 suppression by PJ34 contributes to its anti-breast cancer activity. Together, these results suggest that KIFC1 is a novel promising therapeutic target for breast cancer.

Keywords: KIFC1; PJ34; breast cancer; centrosome clustering; drug target.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Gene Expression / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Molecular Targeted Therapy
  • Phenanthrenes / pharmacology

Substances

  • Antineoplastic Agents
  • N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
  • Phenanthrenes
  • human spleen, embryo, and testes expressed protein, human
  • Kinesin