title: Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells.
abstract: Aberrant regulation of the Wnt/β-catenin pathway has an important role during the onset and progression of colorectal cancer, with over 90% of cases of sporadic colon cancer featuring mutations in APC or β-catenin. However, it has remained a point of controversy whether these mutations are sufficient to activate the pathway or require additional upstream signals. Here we show that colorectal tumours express elevated levels of Wnt3 and Evi/Wls/GPR177. We found that in colon cancer cells, even in the presence of mutations in APC or β-catenin, downstream signalling remains responsive to Wnt ligands and receptor proximal signalling. Furthermore, we demonstrate that truncated APC proteins bind β-catenin and key components of the destruction complex. These results indicate that cells with mutations in APC or β-catenin depend on Wnt ligands and their secretion for a sufficient level of β-catenin signalling, which potentially opens new avenues for therapeutic interventions by targeting Wnt secretion via Evi/Wls.
authors.affiliation: 1] German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany [2].
authors.forename: Oksana
authors.initials: O
authors.lastname: Voloshanenko
authors.forename: Gerrit
authors.initials: G
authors.lastname: Erdmann
authors.forename: Taronish D
authors.initials: TD
authors.lastname: Dubash
authors.forename: Iris
authors.initials: I
authors.lastname: Augustin
authors.forename: Marie
authors.initials: M
authors.lastname: Metzig
authors.forename: Giusi
authors.initials: G
authors.lastname: Moffa
authors.forename: Christian
authors.initials: C
authors.lastname: Hundsrucker
authors.forename: Grainne
authors.initials: G
authors.lastname: Kerr
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandmann
authors.forename: Benedikt
authors.initials: B
authors.lastname: Anchang
authors.forename: Kubilay
authors.initials: K
authors.lastname: Demir
authors.forename: Christina
authors.initials: C
authors.lastname: Boehm
authors.forename: Svenja
authors.initials: S
authors.lastname: Leible
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Ball
authors.forename: Hanno
authors.initials: H
authors.lastname: Glimm
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D009154:Mutation; D009368:Neoplasm Transplantation; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D060508:Wnt3 Protein / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C549111:WLS protein, human; C555507:WNT3 protein, human; D060508:Wnt3 Protein; D051176:beta Catenin; C586310:EPHB2 protein, human; D036183:Receptor, EphB2