The Wnt/β-catenin/VASP positive feedback loop drives cell proliferation and migration in breast cancer

Previous studies have shown that the main function of VASP is to regulate the cytoskeleton and play an important role in promoting tumor cell metastasis. In this study, we first reveal that VASP is located in the nucleus of breast cancer cells and elucidate a Wnt/β-catenin/VASP positive feedback loo...

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Bibliographic Details
Published in:Oncogene 2020-03, Vol.39 (11), p.2258-2274
Main Authors: Li, Kai, Zhang, Jingwei, Tian, Yihao, He, Yanqi, Xu, Xiaolong, Pan, Wenting, Gao, Yang, Chen, Fangfang, Wei, Lei
Format: Article
Language:English
Subjects:
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Apoptosis
Breast cancer
Breast Neoplasms - genetics
c-Myc protein
Cell Adhesion Molecules - metabolism
Cell Biology
Cell migration
Cell Movement
Cell Proliferation
Cyclin D1
Cytoskeleton
Dishevelled protein
Feedback
Female
Human Genetics
Humans
Internal Medicine
Medicine
Medicine & Public Health
Metastases
Microfilament Proteins - metabolism
Myc protein
Oncology
Phosphoproteins - metabolism
Proteins
Signal transduction
Tcf4 protein
Wnt protein
Wnt Signaling Pathway - genetics
β-Catenin
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Summary:Previous studies have shown that the main function of VASP is to regulate the cytoskeleton and play an important role in promoting tumor cell metastasis. In this study, we first reveal that VASP is located in the nucleus of breast cancer cells and elucidate a Wnt/β-catenin/VASP positive feedback loop. We identify that VASP is a target gene of Wnt/β-catenin signaling pathway, and activation of Wnt/β-catenin signaling pathway can significantly upregulate VASP protein expression, while upregulated VASP protein can in turn promote translocation of β-catenin and DVL3 proteins into the nucleus. In the nucleus, VASP, DVL3, β-catenin, and TCF4 can form VASP/DVL3/β-catenin/TCF4 protein complex, activating Wnt/β-catenin signaling pathway, and promoting the expression of target genes VASP, c-myc, and cyclin D1. Thus, our study reveals that there is a Wnt/β-catenin/VASP malignant positive feedback loop in breast cancer, which promotes the proliferation and migration of breast cancer cells, and breaking this positive feedback loop may provide new strategy for breast cancer treatment.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-019-1145-3