Autophagy and the Wnt signaling pathway: A focus on Wnt/β-catenin signaling

Abstract

Cellular homeostasis and adaptation to various environmental conditions are importantly regulated by the sophisticated mechanism of autophagy and its crosstalk with Wnt signaling and other developmental pathways. Both autophagy and Wnt signaling are involved in embryogenesis and differentiation. Autophagy is responsible for degradation and recycling of cytosolic materials by directing them to lysosomes through the phagophore compartment. A dual feedback mechanism regulates the interface between autophagy and Wnt signaling pathways. During nutrient deprivation, β-catenin and Dishevelled (essential Wnt signaling proteins) are targeted for autophagic degradation by LC3. When Wnt signaling is activated, β-catenin acts as a corepressor of one of the autophagy proteins, p62. In contrast, another key Wnt signaling protein, GSK3β, negatively regulates the Wnt pathway and has been shown to induce autophagy by phosphorylation of the TSC complex. This article reviews the interplay between autophagy and Wnt signaling, describing how β-catenin functions as a key cellular integration point coordinating proliferation with autophagy, and it discusses the clinical importance of the crosstalk between these mechanisms.

Keywords: Autophagy; Differentiation; Regulatory feedback mechanism; Wnt signaling pathway.