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

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.

Keywords: Wnt3a; centriolar satellites; multidrug-resistant tumor cell; primary ciliogenesis; β-catenin p-S47.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Casein Kinases / metabolism
  • Centrioles / metabolism*
  • Centrosome / metabolism
  • Cilia / metabolism*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Epitopes / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Ligands
  • MCF-7 Cells
  • Mice
  • Organogenesis*
  • Phosphorylation
  • Phosphoserine / metabolism
  • Wnt3A Protein / chemistry
  • Wnt3A Protein / metabolism*
  • beta Catenin / metabolism*

Substances

  • Epitopes
  • Ligands
  • Wnt3A Protein
  • beta Catenin
  • Phosphoserine
  • Casein Kinases