β-Catenin tumour-suppressor activity depends on its ability to promote Pro-N-Cadherin maturation

Neural stem cells (NSCs) form a pseudostratified, single-cell layered epithelium with a marked apico-basal polarity. In these cells, {beta}-Catenin associates with classic cadherins in order to form the apical adherens junctions (AJs). We previously reported that oncogenic forms of {beta}-Catenin (s{beta}-Catenin) maintain neural precursors as progenitors, while also enhancing their polarization and adhesiveness, thereby limiting their malignant potential. Here we show that {beta}-Catenin can bind to phosphorylated Pro-N-Cadherin, promoting the excision of the propeptide and its maturation into N-Cadherin in the trans-Golgi network (TGN). Moreover, {beta}-Catenin-assisted maturation of Pro-N-Cadherin is required for the formation of the AJs and for them to recruit other apical complex (AC) components like aPKC, and accordingly, to establish apico-basal polarity. Notably, we show that NSCs expressing unprocessed Pro-N-Cadherin invade the ventricle and they breach the basement membrane to invade the surrounding mesenchyme. Hence, we propose that the tumour-suppressor activity of s{beta}-Catenin depends on it promoting Pro-N-Cadherin processing.