Citation Spotlight: Wnt5a regulation of RhoA-mediated remodeling of actin cytoskeleton to control ESCC cell motility

Recently, Wu et al. investigated if Wnt5a signaling affects migration of esophageal squamous cell carcinoma (ESCC) cells and the molecular pathways underlying any Wnt5a-mediated effects. Wnt5a regulates the motility and invasive behavior of breast cancer and glioblastoma cells. A potential role for Wnt5a in ESCC cell migration remained to be demonstrated. Using a variety of pharmacological, molecular, cellular, and biochemical techniques, the authors establish that Wnt5a positively regulates the in vitro invasive behavior of multiple ESCC cell lines. Specifically, Wnt5a expression is up-regulated in invasive tumor tissues (versus non-invasive tumor tissues), resulting in activation of the Wnt5a receptors, ROR1/2 (receptor tyrosine kinase-like orphan receptor 1/2). These changes are the first steps in the sequential activation of a signaling cascade consisting of DAAM1 (disheveled 2/disheveled-associated activator of morphogenesis 1), the GTPase RhoA (but not Rac1, Rac2, or Cdc42), and finally RhoA-mediated re-organization of the actin cytoskeleton. Importantly, ESCC cell invasion requires the participation of each protein component in the above signaling cascade. Cytoskeleton’s RhoA, Rac1,2,3, and Cdc42 G-LISA activation assay kits (Cat. # BK121, BK125, and BK127, respectively) were essential reagents in this study which identified ROR1/2 as novel targets for therapeutic intervention in multiple cancers.