Wnt3a Stimulation Promotes Primary Ciliogenesis through β-Catenin Phosphorylation-Induced Reorganization of Centriolar Satellites

被引:32
|
作者
Kyun, Mi-Lang [1 ,6 ]
Kim, Sun-Ok [1 ]
Lee, Hee Gu [2 ,6 ]
Hwang, Jeong-Ah [3 ]
Hwang, Joonsung [1 ]
Soung, Nak-Kyun [1 ]
Cha-Molstad, Hyunjoo [1 ]
Lee, Sangku [1 ]
Kwon, Yong Tae [4 ,5 ]
Kim, Bo Yeon [1 ,6 ]
Lee, Kyung Ho [1 ]
机构
[1] KRIBB, Anticanc Agent Res Ctr, 30 Yeongudanji Ro, Cheongwon 28116, Chungbuk, South Korea
[2] Korea Res Inst Biosci & Biotechnol, Immunotherapy Convergence Res Ctr, Daejeon 34141, South Korea
[3] Chungnam Natl Univ, Res Inst Med Sci, Dept Physiol, Coll Med, Daejeon, South Korea
[4] Seoul Natl Univ, Coll Med, Prot Metab Med Res Ctr, Seoul, South Korea
[5] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea
[6] Univ Sci & Technol, Dept Biomol Sci, Daejeon 34113, South Korea
来源
CELL REPORTS | 2020年 / 30卷 / 05期
关键词
PRIMARY CILIA; BBS PROTEINS; EXPRESSION; DOMAIN; ROLES;
D O I
10.1016/j.celrep.2020.01.019
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Primary cilium is an antenna-like microtubule-based cellular sensing structure. Abnormal regulation of the dynamic assembly and disassembly cycle of primary cilia is closely related to ciliopathy and cancer. The Wnt signaling pathway plays a major role in embryonic development and tissue homeostasis, and defects in Wnt signaling are associated with a variety of human diseases, including cancer. In this study, we provide direct evidence of Wnt3a-induced primary ciliogenesis, which includes a continuous pathway showing that the stimulation of Wnt3a, a canonical Wnt ligand, promotes the generation of beta-catenin p-S47 epitope by CK1 delta, and these events lead to the reorganization of centriolar satellites resulting in primary ciliogenesis. We have also confirmed the application of our findings in MCF-7/ADR cells, a multidrug-resistant tumor cell model. Thus, our data provide a Wnt3a-induced primary ciliogenesis pathway and may provide a clue on how to overcome multidrug resistance in cancer treatment.
引用
收藏
页码:1447 / +
页数:21
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