Wnt3a suppresses Wnt/β-catenin signaling and cancer cell proliferation following serum deprivation
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092 (China)
- Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120 (China)
- Department of Vascular Surgery, East Hospital, Tongji University School of Medicine, Shanghai 200120 (China)
- Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong 518055 (China)
- Department of Stomatology, Huashan Hospital, Fudan University, Shanghai 200040 (China)
Canonical Wnt/β-catenin signaling is often aberrantly activated in tumor cells and required for tumor growth. The internalization of Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) induced by Wnt ligands is commonly thought to be critical for Wnt/β-catenin signaling activation. However, in contrast to theses previous studies, we here show that persistent excessive stimulation with a canonical Wnt ligand Wnt3a could induce a long-term decreased expression level of membrane LRP6, which prevented nuclear β-catenin accumulation and tumor cell;proliferation. Importantly, Wnt3a was robustly upregulated following serum deprivation. The upregulated Wnt3a under serum deprivation was responsible for LRP6 internalization, decreased accumulation of nuclear β-catenin, and further inhibition of tumor cell proliferation. It has well been known that insufficient blood supply during tumor development occurs frequently, causing a worsening environment for tumor growth. Therefore, these results reveal a novel inhibitory role of Wnt3a on canonical Wnt/β-catenin signaling and cancer cell proliferation when there is an insufficient blood supply during tumor development, which might be a potential mechanism for tumor evasion within a worsening environment. - Highlights: • Wnt3a has a novel inhibitory role on Wnt/β-catenin signaling in cancer cells. • Persistent excessive Wnt3a stimulation suppressed β-catenin and cell proliferation. • Inhibitory effects of Wnt3a were mediated by LRP6 endocytosis. • Inhibitory effects of Wnt3a were abolished by Nystatin or FilipinIII. • Serum deprivation suppressed cell proliferation via elevating Wnt3a expression.
- OSTI ID:
- 22746408
- Journal Information:
- Experimental Cell Research, Vol. 341, Issue 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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