Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer cell migration.
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.


RESULTS
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
Taken together, we demonstrated for the first time that Wnt5a promotes breast cancer cell migration via Dvl2/Daam1/RhoA.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
Yichao
Y
Zhu
Yinhui
Y
Tian
Jun
J
Du
Zhenzhen
Z
Hu
Ling
L
Yang
Jiaojing
J
Liu
Luo
L
Gu
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D000072261:Dishevelled Proteins; D005260:Female; D006801:Humans; D008840:Microfilament Proteins; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C499094:DAAM1 protein, human; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein