title: Wnt3a suppresses Wnt/β-catenin signaling and cancer cell proliferation following serum deprivation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: He
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yan
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Da
authors.initials: D
authors.lastname: Wo
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Limei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Vascular Surgery, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ge
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, Guangdong 518055, China.
authors.forename: Huashun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Stomatology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: shangfengliufudan@163.com.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: 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. Electronic address: wzhu@tongji.edu.cn.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060509:Wnt3A Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin
keywords: Cancer cell; Proliferation; Serum deprivation; Wnt/β-catenin; Wnt3a