Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Aberrant activation of Wnt signalling has an important function in the onset and progression of colorectal cancer. Sporadic colorectal carcinomas are associated with mutations in APC or β-catenin, leading to a constitutive activation by preventing the degradation of β-catenin, allowing its accumulation in the nucleus and drive the expression of transcriptional target for growth and proliferation. While mutations in APC or β-catenin are found in almost all cases of sporadic colon cancer, the molecular circuits that control Wnt signalling pathways in colon cancer cells have not been fully resolved. Here we show that colon cancer cells require Wnt secretion for survival. We combined RNAi-mediated depletion of signalling factors and transcriptional profiling to map the topology of Wnt pathways. We demonstrate that Evi/Wls, a protein required for the secretion of Wnt proteins, impairs the expression of β-catenin dependent transcriptional targets. Blocking Wnt secretion is sufficient to inhibit Wnt signalling and cell survival of colon cancer cell lines ex vivo and in vivo, independent of their APC and β-catenin mutational status. We conclude that mutations in APC and β-catenin in colon cancer do not render colon cancers independent of autocrine activation through Wnt ligands. These results may open new avenues for therapeutic interventions in colon cancer by antagonists of Wnt signalling that act at or upstream of the receptor level.</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3242. doi:1538-7445.AM2012-3242</jats:p>