TOPK is highly expressed in circulating tumor cells, enabling metastasis of prostate cancer

Oncotarget. 2015 May 20;6(14):12392-404. doi: 10.18632/oncotarget.3630.

Abstract

Circulating tumor cells (CTCs) are important for metastasis in prostate cancer. T-LAK cell-originated protein kinase (TOPK) is highly expressed in cancer cells. Herein, we established a xenograft animal model, isolated and cultured the CTCs, and found CTCs have significantly greater migratory capacity than parental cells. TOPK is more highly expressed in the CTCs than in parental cells and is also highly expressed in the metastatic nodules caused by CTCs in mice. Knocking down TOPK decreased the migration of CTCs both in vitro and in vivo. TOPK was modulated by the PI3K/PTEN and ERK pathways during the metastasis of prostate cancer. High levels of TOPK in the tumors of patients were correlated with advanced stages of prostate cancer, especially for high-risk patients of Gleason score≥8, PSA>20ng/ml. In summary, TOPK was speculated to be one of a potential marker and therapeutic target in advanced prostate cancer.

Keywords: T-LAK cell-originated protein kinase (TOPK); circulating tumor cells; metastasis; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / biosynthesis*
  • Neoplasm Invasiveness / pathology*
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology*
  • Prostatic Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase