title: YAP and WWTR1: New targets for skin cancer treatment.
abstract: The core components of the Hippo signaling pathway are a cascade of kinases that govern the phosphorylation of downstream transcriptional co-activators, namely, YES-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ). The Hippo signaling pathway is considered an important tumor-suppressor pathway, and its dysregulation has been noted in a variety of human cancers, in which YAP/WWTR1 enable cancerous cells to overcome contact inhibition, and to grow and spread uncontrollably. Interestingly, however, recent studies have told a somewhat different but perhaps more intriguing YAP/WWTR1 story, as these studies found that YAP/WWTR1 function as a central hub that integrates signals from multiple upstream signaling pathways, cell-cell interactions and mechanical forces and then bind to and activate different downstream transcriptional factors to direct cell social behavior and cell-cell interactions. In this review, we present the latest findings on the role of YAP/WWTR1 in skin physiology, pathology and tumorigenesis and discuss the statuses of newly developed therapeutic interventions that target YAP/WWTR1 in human cancers, as well as their prospects for use as skin cancer treatments.
authors.affiliation: Burnett School of Biological Sciences, University of Central Florida, Orlando, FL 32816, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Andl
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Linli
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Dermatology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Kadekaro
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA. Electronic address: yuhang.zhang@uc.edu.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C456659:YY1AP1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Cancer; Hippo signaling; Skin; Therapeutics; WWTR1; YAP