Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk

Katy J Petherick, Ann C Williams, Jon D Lane, Paloma Ordonez-Moran,JoergHuelsken, Tracey J Collard,Helena JM Smartt, Jennifer Batson,Karim Malik, Chris Paraskeva, and AlexanderGreenhough. EMBO.2013; 32:1903–1916

Speaker: Wan-Ting Kuo (郭琬婷)                   Time: 13:00~14:00, Oct. 16, 2013

Commentator: Dr. Chih-Peng Chang (張志鵬老師)     Place: Room 601

Abstract:

The Wnt/β-catenin pathway plays a crucial role in tumorigenesis and is aberrantly activated in the majority of colorectal tumors.β-cateninassociates with TCF/LEF complex and drives target genes to promote cell proliferation (1). In addition to its role in cell proliferation, β-catenin also can facilitate adaptation to microenvironmental conditions, including hypoxia and oxidative stress (2,3). Another adaptive response to microenvironmental stresses is autophagy, a vital mechanism for recycling cytosolic components to maintain homeostasis (4). It is essential to balance between proliferation and autophagy under various conditions, but the underlying mechanism remains unclear. In this report, the authors demonstrated that β-catenin suppressesed autophagy and repressed the expression of the autophagy adaptor p62 at transcriptional level. The authors further showed that during nutrient deprivation, β-catenin selectively formed a β-catenin-LC3 complex and degraded by proteasome-independent manner. They found that β-catenin W/YXXI/L motif (LC3-interacting region) interacted with LC3 and was degraded via the lysosome degradation mechanism. Furthermore, β-catenin/TCF-driven transcription and cell proliferation were attenuated. In summary, despite Wnt/β-catenin represses autophagy and p62 expression. β-catenin could be targeted by LC3 for degradation while autophagy was induction. The authors reveal a regulatory feedback mechanism between β-catenin and autophagy and place β-catenin at a key cellular integration point coordinating proliferation with autophagy. Their findings implicate these pathway can be targeted for cancer therapy.

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