EACR poster prize winner for "Autolysosomal β-catenin degradation regulates Wnt-autophagy/p62 crosstalk"

Greenhough, Alexander

Abstract

(EACR Poster Prize) The Wnt/β-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/β-catenin signalling pathway as a negative regulator of both basal and stress-induced autophagy. Manipulation of β-catenin expression levels in vitro and in vivo revealed that β-catenin suppresses autophagosome formation and directly represses p62/SQSTM1 (encoding the autophagy adaptor p62) via TCF4. Furthermore, we show that during nutrient deprivation β-catenin is selectively degraded via the formation of a β-catenin-LC3 complex, attenuating β-catenin/TCF-driven transcription and proliferation to favour adaptation during metabolic stress. Formation of the β-catenin-LC3 complex is mediated by a W/YXXI/L motif and LC3-interacting region (LIR) in β-catenin, which is required for interaction with LC3 and non-proteasomal degradation of β-catenin. Thus, Wnt/β-catenin represses autophagy and p62 expression, while β-catenin is itself targeted for autophagic clearance in autolysosomes upon autophagy induction. These findings reveal a regulatory feedback mechanism that place β-catenin at a key cellular integration point coordinating proliferation with autophagy, with implications for targeting these pathways for cancer therapy.

• Presentation Conference Type: Poster
• Conference Name: 29th Genes & Cancer Conference
• Start Date: Dec 8, 2012
• End Date: Dec 10, 2012
• Acceptance Date: Dec 8, 2012
• Peer Reviewed: Not Peer Reviewed
• Public URL: https://uwe-repository.worktribe.com/output/941256
• Additional Information: Title of Conference or Conference Proceedings : 29th Genes & Cancer Conference