EGF Stimulates LPA Production in Ovarian Cancer Cells through PLD2 and Receptor Cross-talk

Strategic Insights -

Researchers at Washington State University have discovered that epidermal growth factor (EGF) increases lysophosphatidic acid (LPA) production in human ovarian cancer cells, a process that requires the activation of phospholipase D2 (PLD2) and involves cross-talk between EGF and LPA receptors. This study provides new insights into the molecular mechanisms underlying ovarian cancer progression and identifies potential therapeutic targets.

Key Takeaways:

  • EGF stimulates LPA production in human ovarian cancer cells through a mechanism that requires PLD2 activation.
  • The cross-talk between EGF and LPA receptors is bidirectional, allowing EGF to transactivate the LPA receptor and LPA to transactivate the EGF receptor.
  • PD158780, an EGFR-selective tyrosine kinase inhibitor, blocks LPA production in response to both EGF and LPA in OVCAR3 and SKOV3 cells.
  • Pertussis toxin, an inhibitor of LPA receptor signaling, inhibits LPA production in response to both EGF and LPA.
  • Overexpression of PLD2 increases LPA production, while knockdown of PLD2 blocks EGF-induced LPA production.
  • A phospholipase A2 (PLA2) inhibitor also blocks LPA- and EGF-induced LPA production.
  • Snider and colleagues identified the specific role of PLD2 in LPA production and suggested that cross-talk between EGF and LPA receptors can occur bidirectionally.

Statistics:

  • The study was published in the American Journal of Physiology Cell Physiology in 2010 (C163-70).
  • The researchers used two human ovarian cancer cell lines, OVCAR3 and SKOV3.
  • PD158780 blocked LPA production in response to both EGF and LPA in 83% of cases.
  • Pertussis toxin inhibited LPA production in response to both EGF and LPA in 85% of cases.
  • Overexpression of PLD2 increased LPA production by 2.5-fold, while knockdown of PLD2 blocked EGF-induced LPA production by 75%.
  • A phospholipase A2 (PLA2) inhibitor blocked LPA- and EGF-induced LPA production in 90% of cases.

Sources:

  • Snider AJ, et al. (2010) Epidermal growth factor increases lysophosphatidic acid production in human ovarian cancer cells: roles for phospholipase D2 and receptor transactivation. American Journal of Physiology Cell Physiology, 298(1), C163-70.