Title: Targeting RhoA/Rho Kinase and p21-Activated Kinase Signaling to Prevent Cancer Development and Progression
Volume: 4
Issue: 2
Author(s): Yu-Wen E. Chang, Ronald R. Bean and Rolf Jakobi
Affiliation:
Keywords:
Cancer invasion, metastasis, RhoA, Rho kinase, ROCK, p21-activated kinase, PAK, adherens junctions, cell motility, apoptosis
Abstract: Elevated RhoA/Rho kinase and p21-activated kinase signaling have been shown to promote cancer development and metastasis and have drawn much attention as potential targets of anti-cancer therapy. Elevated RhoA and Rho kinase activity promote cancer cell invasion and eventually lead to metastasis by disrupting E-cadherin-mediated adherens junctions and degradation of the extracellular matrix. Elevated p21-activated kinase activity promotes invasion by stimulating cell motility but also promotes cancer cell survival and growth. In this review we describe normal functions of RhoA/Rho kinase and p21-activated kinase signaling, mechanisms that lead to constitutive activation of RhoA/Rho kinase and p21-activated kinase pathways, and processes by which constitutive RhoA/Rho kinase and p21-activated kinase activity promote cancer development and progression to more aggressive and metastatic phenotypes. In addition, we summarize relevant patents on RhoA/Rho kinase and p21-activated kinase as targets of anti-cancer therapy and discuss the clinical potential of different approaches to modulate RhoA/Rho kinase and p21-activated kinase signaling.
