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

Abstract

Summary: 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. : Kyun et al. report a continuous primary ciliogenesis pathway showing that Wnt3a stimulation activates CK1δ and active CK1δ phosphorylates β-catenin, which then leads to the reorganization of centriolar satellites resulting in primary ciliogenesis. They also confirm the relevance of this pathway in multidrug-resistant tumor cells. Keywords: Wnt3a, primary ciliogenesis, β-catenin p-S47, centriolar satellites, multidrug-resistant tumor cell