biostudies-literatureUnknown109(8)Bonnans Cβ-Arrestins (Arrb) participate in the regulation of multiple signaling pathways, including Wnt/β-catenin, the major actor in human colorectal cancer initiation. To better understand the roles of Arrb in intestinal tumorigenesis, a reverse genetic approach (Arrb(-/-)) and in vivo siRNA treatment were used in Apc(Δ14/+) mice. Mice with Arrb2 depletion (knockout and siRNA) developed only 33% of the tumors detected in their Arrb2-WT littermates, whereas Arrb1 depletion remained without significant effect. These remaining tumors grow normally and are essentially Arrb2-independent. Unsupervised hierarchical clustering analysis showed that they clustered with 25% of Apc(Δ14/+);Arrb2(+/+) tumors. Genes overexpressed in this subset reflect a high interaction with the immune system, whereas those ovProceedings of the National Academy of Sciences of the United States of America3047-52https://www.ebi.ac.uk/biostudies/studies/S-EPMC3286958biostudies-literatureEssential requirement for β-arrestin2 in mouse intestinal tumors with elevated Wnt signaling.PMC3286958Crespy PSeverac DDesvignes JPBonnans CFlaceliere MHollande FEscriou VGrillet FJournot LDantec CBibeau FPannequin JJoubert DDubois EfalseEssential requirement for β-arrestin2 in mouse intestinal tumors with elevated Wnt signaling.β-Arrestins (Arrb) participate in the regulation of multiple signaling pathways, including Wnt/β-catenin, the major actor in human colorectal cancer initiation. To better understand the roles of Arrb in intestinal tumorigenesis, a reverse genetic approach (Arrb(-/-)) and in vivo siRNA treatment were used in Apc(Δ14/+) mice. Mice with Arrb2 depletion (knockout and siRNA) developed only 33% of the tumors detected in their Arrb2-WT littermates, whereas Arrb1 depletion remained without significant effect. These remaining tumors grow normally and are essentially Arrb2-independent. Unsupervised hierarchical clustering analysis showed that they clustered with 25% of Apc(Δ14/+);Arrb2(+/+) tumors. Genes overexpressed in this subset reflect a high interaction with the immune system, whereas those ov2012-01-01T00:00:00Z2012 Feb2026-04-30T10:45:00.964Z2026-04-07T15:59:28.054ZS-EPMC32869582231540310.1073/pnas.1109457109