Journal
CELLULAR SIGNALLING
Volume 25, Issue 5, Pages 1075-1085Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.01.015
Keywords
Rab35; Rac1; Wnt5a; Dvl2; Breast cancer; Migration
Categories
Funding
- National Natural Science Foundation of China [81172002, 81101999]
- State Key Laboratory of Reproductive Medicine
- Nanjing Medical University
- Natural Science Foundation of Jiangsu Province [BK2012893]
- Postdoctoral Science Foundation of China [2011M501254, 2012T50484]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Ask authors/readers for more resources
The small GTPases regulate many major biological processes in both tutnorigenesis and tumor progression such as cell survival, actin cytoslceleton organization, cell polarity and movement. Wnt5a, a non-canonical Wnt family member, is implicated in the activation of small GTPases in breast cancer. We previously demonstrated that Wnt5a signaling stimulates the migration of breast cancer cells MDA-MB-231 via activating RhoA. However, we found here that RhoA activation was not enhanced by Wnt5a in breast cancer cells MCF-7. The conflicting results prompted us to further probe novel small GTPases in response to Wnt5a and investigate the mechanisms whereby cell migration is regulated. We showed here that Wnt5a dose dependently activated DvI2, Rab35 and Racl and subsequently promoted the migration of MCF-7 cells, which was, however, abolished by knocking down Wnt5a expression via small interfering RNA (siRNA) transfection. DvI2 siRNA significantly decreased background and Wnt5a-induced Rab35/Racl activation and, consequently, cell migration. Rab35 short hairpin RNA (shRNA) remarkably inhibited background and Wnt5a-induced Racl activation and cell migration. Additionally, blockade of Racl activation with Racl siRNA suppressed background and Wnt5a-induced cell migration. Co-immunoprecipitation and immunofluorescence assays showed that Dvl2 bound to Rab35 in mammalian cells. Taken together, we demonstrated that Wnt5a promotes breast cancer cell migration via the Dvl2/Rab35/Rac1 signaling pathway. These findings implicate Wnt5a signaling in regulating small GTPases, which could be targeted for manipulating breast cancer cell migration. (C) 2013 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available