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

Perez-Castro L, Venkateswaran N, Garcia R, Hao YH, Lafita-Navarro MC, Kim J, Segal D, Saponzik E, Chang BJ, Fiolka R, Danuser G, Xu L, Brabletz T, Conacci-Sorrell M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Journal of Cell Science Company of Biologists

Book Volume: 135

Article Number: jcs260028

Journal Issue: 20

DOI: 10.1242/jcs.260028

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.

Authors with CRIS profile

Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung

Involved external institutions

University of Texas Southwestern Medical Center (UT Southwestern) US United States (USA) (US)

How to cite

APA:

Perez-Castro, L., Venkateswaran, N., Garcia, R., Hao, Y.H., Lafita-Navarro, M.C., Kim, J.,... Conacci-Sorrell, M. (2022). The AHR target gene scinderin activates the WNT pathway by facilitating the nuclear translocation of β-catenin. Journal of Cell Science, 135(20). https://doi.org/10.1242/jcs.260028

MLA:

Perez-Castro, Lizbeth, et al. "The AHR target gene scinderin activates the WNT pathway by facilitating the nuclear translocation of β-catenin." Journal of Cell Science 135.20 (2022).

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