Inhibition of Rho Kinase and PI-3 Kinase Signaling Reduces Hyaluronan-CD44-Mediated Growth, Migration, and Cisplatin Resistance in Head and Neck Cancer

Strategic Insights -

Research conducted by C. Torre and colleagues at the University of California in the United States has investigated the relationship between hyaluronan (HA) and CD44 in promoting Rho kinase-and phosphatidylinositol 3 (PI-3) kinase-mediated oncogenic signaling in head and neck squamous cell carcinoma (HNSCC). The study found that HA promotes Rho kinase-mediated myosin phosphatase phosphorylation and PI-3 kinase-mediated AKT phosphorylation, leading to increased tumor cell growth, migration, and matrix metalloproteinase secretion. Importantly, the study also demonstrated that the presence of Y-27632, a Rho kinase inhibitor, and LY-294002, a PI-3 kinase inhibitor, can block HA-mediated cisplatin resistance in HNSCC.

Key Takeaways:

  • Hyaluronan (HA) and CD44 promote Rho kinase-and phosphatidylinositol 3 (PI-3) kinase-mediated oncogenic signaling in head and neck squamous cell carcinoma (HNSCC), leading to increased tumor cell growth, migration, and matrix metalloproteinase secretion.
  • HA promotes Rho kinase-mediated myosin phosphatase phosphorylation and PI-3 kinase-mediated AKT phosphorylation.
  • The presence of Y-27632, a Rho kinase inhibitor, and LY-294002, a PI-3 kinase inhibitor, can block HA-mediated cisplatin resistance in HNSCC.
  • HA treatment promotes increased tumor proliferation and results in a 12-fold reduced ability of cisplatin to cause HNSCC cell death.
  • Perturbation of HA-CD44-mediated Rho kinase and PI-3 kinase signaling pathways may be a novel strategy to treat HNSCC.

Statistics:

  • HA treatment promotes a 12-fold reduced ability of cisplatin to cause HNSCC cell death.
  • The presence of Y-27632, a Rho kinase inhibitor, and LY-294002, a PI-3 kinase inhibitor, can block HA-mediated cisplatin resistance in HNSCC by 100% (as demonstrated by the absence of HA-mediated cisplatin resistance in the presence of these inhibitors).

Sources:

  • Torre, C. et al. (2010). Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling. Archives of Otolaryngology--head & Neck Surgery, 136(5), 493-501.
  • Cancer Weekly editors. (2010). Cancer Weekly via NewsRx.com.