Targeting RhoA/Rho kinase and p21-activated kinase signaling to prevent cancer development and progression.
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.
Chang
Yu-Wen E
YW
Kansas City University of Medicine and Biosciences, Kansas City, MO 64106-1453, USA. echang@kcumb.edu
Bean
Ronald R
RR
Jakobi
Rolf
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000235:genetics / Q000502:physiology*; D054460:rho-Associated Kinases / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
D000970:Antineoplastic Agents; D015820:Cadherins; D054462:p21-Activated Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein