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Wnt3a 通过 β-连环蛋白磷酸化诱导中心体卫星重排促进初级纤毛发生。

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

机构信息

Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongwon, Chungbuk 28116, Republic of Korea; Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea.

Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongwon, Chungbuk 28116, Republic of Korea.

出版信息

Cell Rep. 2020 Feb 4;30(5):1447-1462.e5. doi: 10.1016/j.celrep.2020.01.019.

Abstract

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 β-catenin p-S47 epitope by CK1δ, 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.

摘要

初级纤毛是一种类似天线的微管细胞感应结构。初级纤毛的动态组装和拆卸周期的异常调节与纤毛病和癌症密切相关。Wnt 信号通路在胚胎发育和组织稳态中起主要作用,Wnt 信号通路的缺陷与多种人类疾病有关,包括癌症。在这项研究中,我们提供了 Wnt3a 诱导的初级纤毛发生的直接证据,包括一条连续的途径,表明经典 Wnt 配体 Wnt3a 的刺激促进 CK1δ 产生 β-连环蛋白 p-S47 表位,这些事件导致中心粒卫星的重排,从而导致初级纤毛发生。我们还证实了我们的发现在 MCF-7/ADR 细胞中的应用,这是一种多药耐药肿瘤细胞模型。因此,我们的数据提供了 Wnt3a 诱导的初级纤毛发生途径,并可能为克服癌症治疗中的多药耐药性提供线索。

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