Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer

• DOI: 10.1038/s41467-019-08586-3
• Publication Date: 2019-02-13T11:05:13Z
• Authors: David M. Gay; Rachel A. Ridgway; Miryam Müller; Michael C. Hodder; Ann Hedley; William Clark; Joshua D. Leach; Rene Jackstadt; Colin Nixon; David J. Huels; Andrew D. Campbell; Thomas G. Bird; Owen J. Sansom
• Keywords: LGR5

Abstract Different thresholds of Wnt signalling are thought to drive stem cell maintenance, regeneration, differentiation and cancer. However, the principle that oncogenic could be specifically targeted remains controversial. Here we examine requirement BCL9/9l, constituents Wnt-enhanceosome, for intestinal transformation following loss tumour suppressor APC. Although required Lgr5+ cells Bcl9/9l deletion has no impact upon normal homeostasis. Loss BCL9/9l suppressed many features acute APC subsequent pathway deregulation in vivo. This resulted a level activation favoured initiation proximal small intestine (SI) blocked growth colon. Furthermore, completely abrogated β-catenin driven hepatocellular transformation. We speculate these results support just-right hypothesis Wnt–driven formation. Importantly, is particularly effective at blocking colonic tumourigenesis mutations most resemble those occur human