title: A YAP/TAZ-Regulated Molecular Signature Is Associated with Oral Squamous Cell Carcinoma.
abstract: Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here, we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive protumorigenic signals in OSCC. Regions of premalignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in protumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology.
  
  
  CONCLUSIONS
  This study defines a YAP/TAZ-regulated transcriptional program in OSCC and reveals novel roles for nuclear YAP/TAZ activity in the onset and progression of this cancer.
authors: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts.
authors: Samantha E
authors: SE
authors: Hiemer
authors: Section of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts.
authors: Liye
authors: L
authors: Zhang
authors: Section of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts. Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America.
authors: Vinay K
authors: VK
authors: Kartha
authors: Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, Massachusetts.
authors: Trevor S
authors: TS
authors: Packer
authors: Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, Massachusetts.
authors: Munirah
authors: M
authors: Almershed
authors: Division of Oral Pathology, Boston University School of Dental Medicine, Boston, Massachusetts.
authors: Vikki
authors: V
authors: Noonan
authors: Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, Massachusetts.
authors: Maria
authors: M
authors: Kukuruzinska
authors: Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, Massachusetts.
authors: Manish V
authors: MV
authors: Bais
authors: Section of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts.
authors: Stefano
authors: S
authors: Monti
authors: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts. xvarelas@bu.edu.
authors: Xaralabos
authors: X
authors: Varelas
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human