NOTUM is a potential pharmacodynamic biomarker of wnt pathway inhibition
Madan, B Ke, Z Lei, Z.D Oliver, F.A Oshima, M Lee, M.A Rozen, S Virshup, D.M
Ke, Z
Oshima, M
Lee, M.A
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Alternative Title
Abstract
Activation of Wnt signaling due to Wnt overexpression or mutations of Wnt pathway components is associated with various cancers. Blocking Wnt secretion by inhibiting PORCN enzymatic activity has shown efficacy in a subset of cancers with elevated Wnt signaling. Predicting response to upstream Wnt inhibitors and monitoring response to therapeutics is challenging due to the paucity of well-defined biomarkers. In this study we identify Notum as a potential biomarker for Wnt driven cancers and show that coordinate regulation of NOTUM and AXIN2 expression may be a useful predictor of response to PORCN inhibitors. Most importantly, as NOTUM is a secreted protein and its levels in blood correlate with tumor growth, it has potential as a pharmacodynamic biomarker for PORCN and other Wnt pathway inhibitors.
Keywords
AXIN2 protein, biological marker, esterase, Notum protein, unclassified drug, acyltransferase, axin, AXIN2 protein, human, esterase, ETC-159, fused heterocyclic rings, membrane protein, Notum protein, human, PORCN protein, human, tumor marker, animal experiment, animal model, Article, autocrine effect, blood analysis, controlled study, in vitro study, in vivo study, intracellular signaling, mouse, nonhuman, prediction, protein determination, protein expression, protein secretion, Wnt signaling pathway, animal, antagonists and inhibitors, Bagg albino mouse, biosynthesis, C57BL mouse, down regulation, drug effects, fibrosarcoma, genetic transfection, human, metabolism, nude mouse, pancreas tumor, tumor cell line, Wnt signaling, xenograft, Acyltransferases, Animals, Axin Protein, Biomarkers, Tumor, Cell Line, Tumor, Down-Regulation, Esterases, Fibrosarcoma, Heterocyclic Compounds, 4 or More Rings, Heterografts, Humans, Membrane Proteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Pancreatic Neoplasms, Transfection, Wnt Signaling Pathway
Source Title
Oncotarget
Publisher
Impact Journals LLC
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Date
2016
DOI
10.18632/oncotarget.7157
Type
Article