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ATF6 promotes colorectal cancer growth and stemness by regulating the Wnt pathway II

GSE274172 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2024/08/08 Platform GPL24676
Summary
The unfolded protein response maintains endoplasmic reticulum (ER) homeostasis by sensing protein-folding stress and orchestrating cellular adaptation via the ER-transmembrane proteins IRE1, PERK and ATF6. Malignant cells can co-opt IRE1 and PERK to sustain growth; however, the importance of ATF6 in cancer remains poorly deciphered. We observed elevated ATF6 transcriptional activity in several cancers including colorectal carcinoma (CRC). Genetic silencing or small molecule inhibition of ATF6 blocked cell cycle progression and reduced viability of several human CRC cell lines in vitro and disrupted tumor progression in vivo. Unexpectedly, ATF6 interference disabled Wnt and Myc signaling and reduced stemness. ATF6 inhibition attenuated growth of organoids derived from malignant but not normal human intestinal tissue, decreasing Wnt-pathway activity and driving cellular differentiation. Wnt-surrogate agonism in a Wnt-dependent CRC organoid restored pathway activity and rescued growth under ATF6 blockade. Our findings identify ATF6 as an unexpected facilitator of oncogenic Wnt signaling in CRC.
Published in
ATF6 Promotes Colorectal Cancer Growth and Stemness by Regulating the Wnt Pathway
Rodvold JJ, Grimmer M, Ruiz K et al. · Cancer research communications 2024 · PMID 39324706 · doi:10.1158/2767-9764.CRC-24-0268
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Also filed as BioProject PRJNA1145347 and SRA study SRP524724. Searching any of these in the dataset finder brings you back here.

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