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CXCL13 mediates prostate cancer cell proliferation through JNK signalling and invasion through ERK activation

C P El-Haibi1, R Singh, P K Sharma

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Cell Proliferation
|June 8, 2011
PubMed
Abstract

Insights

This study reveals dedicator of cytokinesis 2 (DOCK2) is expressed in hormone-refractory prostate cancer (PCa) cells. CXCL13 drives PCa cell invasion via Akt/ERK1/2, and proliferation via JNK, with DOCK2 being crucial for hormone-refractory PCa cell proliferation.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Signaling

Background:

  • Prostate cancer (PCa) progression involves complex signaling pathways.
  • The role of CXCL13 and its downstream effectors in PCa remains incompletely understood, particularly in hormone-refractory disease.

Purpose of the Study:

  • To investigate the signaling molecules dedicator of cytokinesis 2 (DOCK2), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase-1 (JNK), and Akt in CXCL13-mediated PCa cell invasion and proliferation.
  • To differentiate the roles of these pathways in androgen-sensitive versus hormone-refractory PCa cells.

Main Methods:

  • Utilized androgen-sensitive (LNCaP) and hormone-refractory (PC3) PCa cell lines, alongside normal (RWPE-1) cells.
  • Employed immuno-blotting, FACE ELISA, caspase activity assays, and cell invasion/proliferation assays.
  • Assessed signaling events including DOCK2, ERK1/2, JNK, and Akt activation.

Main Results:

  • The hormone-refractory PC3 cell line, unlike LNCaP cells, expresses DOCK2.
  • CXCL13-mediated invasion in both LNCaP and PC3 cells was dependent on Akt and ERK1/2 activation, independent of DOCK2.
  • CXCL13 promoted LNCaP proliferation via JNK (DOCK2-independent) but PC3 proliferation via JNK, requiring DOCK2.

Conclusions:

  • CXCL13-mediated PCa cell invasion necessitates Akt and ERK1/2 activation.
  • DOCK2 plays a significant role in the proliferation of hormone-refractory, CXCR5-positive PCa cells.
  • These findings highlight distinct signaling mechanisms in PCa progression and potential therapeutic targets.

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