title: YAP oncogene overexpression supercharges colon cancer proliferation.
abstract: The transcriptional co-activator YAP is an evolutionarily conserved regulator of organ size and progenitor cell proliferation. YAP is overexpressed at high frequency in many common human cancers and can directly drive cancer development in mouse models. YAP abundance and nuclear localization are negatively regulated by the Hippo kinase cascade, which, in epithelia, is activated by physiological cell-cell contact. Recent work in intestinal epithelium has established that YAP is constitutively inhibited by the Hippo pathway and entirely dispensable for normal development and homeostasis. YAP serves only in a standby capacity; should cell-cell contact be abrogated, as after intestinal damage, the loss of Hippo input permits increased YAP abundance and nuclear residence. In turn, YAP cooperates with β-catenin to transactivate genes that promote stem cell expansion for epithelial repair. This interplay between overexpressed YAP and β-catenin also drives proliferation of colon cancer cells. The dispensability of YAP in normal intestine makes YAP's expression or outputs attractive targets for cancer therapy.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA. avruch@molbio.mgh.harvard.edu
authors.forename: Joseph
authors.initials: J
authors.lastname: Avruch
authors.forename: Dawang
authors.initials: D
authors.lastname: Zhou
authors.forename: Nabeel
authors.initials: N
authors.lastname: Bardeesy
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D010766:Phosphorylation; D059748:Proteolysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D051176:beta Catenin