The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis.
Bottom Line: Malignant astrocytomas are highly aggressive brain tumours with poor prognosis.Evi/Wls is a core Wnt signalling component and a specific regulator of pan-Wnt protein secretion, affecting both canonical and non-canonical signalling.We further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling.
Affiliation: German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany. firstname.lastname@example.orgShow MeSH
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Mentions: Evi is ubiquitously expressed during mouse embryonic development with particular prominent expression in the developing head structures. Expression persists in adult tissues with distinct expression pattern and levels in different organs (Jin et al, 2010; Yu et al, 2010; our unpublished data). Evi is essential for Wnt-dependent developmental processes (Fu et al, 2009). To assess Evi expression during brain tumourigenesis, we analysed an expression profiling database of 71 diffuse astrocytic tumours of different malignancy grades [WHO grade II: n = 8; WHO grade III: n = 11; WHO grade IV (primary glioblastoma: n = 42 and secondary glioblastoma: n = 10)] (Toedt et al, 2011). Strikingly, we found that Evi is strongly overexpressed in astrocytic gliomas of all malignancy grades as compared to control tissue (Fig 1A). This finding was confirmed in an independent data set from the Molecular Brain Neoplasia Database (REMBRANDT) (Madhavan et al, 2009), which also revealed a significant upregulation of Evi transcripts in gliomas. Moreover, higher levels of Evi expression were associated with shorter overall survival of glioma patients (p = 0.013) (Fig S1 of Supporting information). Evi expression levels showed no association with gender, age, TP53, IDH1 or IDH2 mutation status or with MGMT promoter methylation status (data not shown).
Affiliation: German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany. email@example.com