title: Genomic insights into WNT/β-catenin signaling.
abstract: The canonical WNT pathway regulates the stability of the proto-oncogene β-catenin and is aberrantly activated in many cancer types. Studies in a wide range of experimental models confirm that β-catenin activity is required for tumor initiation in cancers where this pathway is deregulated. However, to date this pathway has proven to be challenging to target therapeutically. Moreover, several lines of evidence suggest that other components and regulators of β-catenin exist. Here we will describe recent structural and functional studies describing genomic alterations and new regulators of β-catenin that lead to aberrant activation of the WNT/β-catenin pathway. These findings provide new insights into the biology of WNT/β-catenin signaling and suggest potential therapeutic opportunities.
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142 USA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215 USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenbluh
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142 USA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215 USA.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142 USA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215 USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 USA. Electronic address: William_Hahn@dfci.harvard.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
mesh_terms: D000818:Animals; D006801:Humans; D000090063:Proto-Oncogene Mas; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051153:Wnt Proteins; D051176:beta Catenin
keywords: WNT; YAP1; cancer; synthetic lethality; β-catenin