b-catenin 南京医科大学(英文版).pdfVIP

Dvl2-Dependent Activation of Daam1 and RhoA Regulates Wnt5a-Induced Breast Cancer Cell Migration 1,2 3 1,2 3 4 3 1,2 Yichao Zhu , Yinhui Tian , Jun Du , Zhenzhen Hu , Ling Yang , Jiaojing Liu , Luo Gu * 1 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China, 2 Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China, 3 Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China, 4 Department of Cardiology, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China Abstract Background: The Dishevelled (Dvl) and Dishevelled-associated activator of morphogenesis 1 (Daam1) pathway triggered by Wnt5a regulates cellular polarity during development and tissue homoeostasis. However, Wnt5a signaling in breast cancer progression remains poorly defined. Methodology/Principal Findings: We showed here that Wnt5a activated Dvl2, Daam1 and RhoA, and promoted migration of breast cancer cells, which was, however, abolished by Secreted Frizzled-related protein 2 (sFRP2) pretreatment. Dominant negative Dvl2 mutants or Dvl2 siRNA significantly decreased Wnt5a-induced Daam1/RhoA activation and cell migration. Ectopic expression of N-Daam1, a dominant negative mutant, or Daam1 siRNA remarkably inhibited Wnt5a-induced RhoA activation, stress fiber formation and cell migration. Ectopic expression of dominant negative RhoA (N19) or C3 exoenzyme transferase, a Rho inhibitor, decreased Wnt5a-induced stress fiber formation and cell migration. Conclusions/Significance: Taken together, we demonstrated for the first time that Wnt5a promotes breast cancer cell migration via Dvl2/Daam1/RhoA.