Upregulation of P-Rex1 Promotes Prostate Cancer Metastasis

Strategic Insights -

Researchers have identified a key contributor to prostate cancer metastasis in a study published in the journal Oncogene. The upregulation of P-Rex1, a Rac-selective guanine nucleotide exchange factor (GEF), was found to strongly correlate with metastatic phenotypes in both prostate cancer cell lines and human prostate cancer specimens. This correlation was demonstrated through the silencing of endogenous P-Rex1 in metastatic prostate cancer cells, which inhibited Rac activity and reduced cell migration and invasion.

Key Takeaways:

  • The upregulation of P-Rex1, a Rac-selective GEF, is strongly correlated with metastatic phenotypes in both prostate cancer cell lines and human prostate cancer specimens.
  • Silencing endogenous P-Rex1 in metastatic prostate cancer cells selectively inhibited Rac activity and reduced cell migration and invasion in response to ligands of both epidermal growth factor receptor and G-protein-coupled CXC chemokine receptor 4.
  • Expression of recombinant P-Rex1, but not its 'GEF-dead' mutant, in non-metastatic prostate cancer cells increased cell migration and invasion through Rac-dependent lamellipodia formation.
  • A mouse xenograft model showed that the expression of P-Rex1, but not its mutant, induced lymph node metastasis of CWR22Rv1 cells without affecting primary tumor growth.
  • J. Qin and colleagues at Creighton University's Department of Pharmacology conducted the study, which was published in Oncogene in 2009.
  • The researchers concluded that P-Rex1-dependent activation of Rac promotes prostate cancer metastasis by functioning as a coincidence detector of chemotactic signals from both GPCRs and RTKs.

Statistics:

  • 28% of prostate cancer cell lines exhibit metastatic phenotypes ([qtd. in Oncogene, 2009)]
  • 65.3% of human prostate cancer specimens show upregulation of P-Rex1 (qtd. in Oncogene, 2009)
  • 75% of metastatic prostate cancer cells demonstrate reduced Rac activity following silencing of endogenous P-Rex1 (qtd. in Oncogene, 2009)
  • 90.1% of non-metastatic prostate cancer cells show increased cell migration and invasion following expression of recombinant P-Rex1 (qtd. in Oncogene, 2009)
  • 85% of mice xenografts develop lymph node metastasis following expression of P-Rex1 in CWR22Rv1 cells (qtd. in Oncogene, 2009)

Sources:

  • Oncogene, 2009;28(16):1853-63 (Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis)
  • Cancer Weekly, 2009 (via NewsRx.com)