The AHR target gene scinderin activates the WNT pathway by facilitating the nuclear translocation of β-catenin

Lizbeth Perez-Castro, Niranjan Venkateswaran, Roy Garcia, Yi Heng Hao, M. C. Lafita-Navarro, Jiwoong Kim, Dagan Segal, Etai Saponzik, Bo Jui Chang, Reto P Fiolka, Gaudenz Danuser, Lin Xu, Thomas Brabletz, Maralice Conacci-Sorrell

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) regulates cellular detoxification, proliferation and immune evasion in a range of cell types and tissues, including cancer cells. In this study, we used RNA-sequencing to identify the signature of the AHR target genes regulated by the pollutant 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and the endogenous ligand kynurenine (Kyn), a tryptophan-derived metabolite. This approach identified a signature of six genes (CYP1A1, ALDH1A3, ABCG2, ADGRF1 and SCIN) as commonly activated by endogenous or exogenous ligands of AHR in multiple colon cancer cell lines. Among these, the actin-severing protein scinderin (SCIN) was necessary for cell proliferation; SCIN downregulation limited cell proliferation and its expression increased it. SCIN expression was elevated in a subset of colon cancer patient samples, which also contained elevated β-catenin levels. Remarkably, SCIN expression promoted nuclear translocation of β-catenin and activates the WNT pathway. Our study identifies a new mechanism for adhesion-mediated signaling in which SCIN, likely via its ability to alter the actin cytoskeleton, facilitates the nuclear translocation of β-catenin. This article has an associated First Person interview with the first authors of the paper.

Original languageEnglish (US)
JournalJournal of cell science
Volume135
Issue number20
DOIs
StatePublished - Oct 15 2022

Keywords

  • Aryl hydrocarbon receptor
  • Colon cancer
  • FICZ
  • Kynurenine
  • TCDD

ASJC Scopus subject areas

  • Cell Biology

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