title: TAZ and YAP are frequently activated oncoproteins in sarcomas.
abstract: TAZ (WWTR1) and YAP are transcriptional coactivators and oncoproteins inhibited by the Hippo pathway. Herein we evaluate 159 sarcomas representing the most prevalent sarcoma types by immunohistochemistry for expression and activation (nuclear localization) of TAZ and YAP. We show that 50% of sarcomas demonstrate activation of YAP while 66% of sarcomas demonstrate activated TAZ. Differential activation of TAZ and YAP are identified in various sarcoma types. At an RNA level, expression of WWTR1 or YAP1 predicts overall survival in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. Immunohistochemistry demonstrates that TAZ and YAP expression and activation are positively correlated with grade in the well-differentiated liposarcoma to dedifferentiated liposarcoma tumor progression sequence as well as conventional chondrosarcomas. TAZ and YAP are constitutively activated oncoproteins in sarcoma cell lines. Knock-down of TAZ and YAP demonstrate differential activity for the two proteins. Verteporfin decreases colony formation in soft agar as well as CTGF expression in sarcoma cell lines harboring activated TAZ and YAP.
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Fullenkamp
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Hall
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Omar I
authors.initials: OI
authors.lastname: Jaber
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Pakalniskis
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Erica C
authors.initials: EC
authors.lastname: Savage
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Savage
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Georgina K
authors.initials: GK
authors.lastname: Ofori-Amanfo
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Allyn M
authors.initials: AM
authors.lastname: Lambertz
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Ivins
authors.affiliation: Department of Biology, University of Iowa, Iowa City, IA, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stipp
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Miller
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Milhem
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Munir R
authors.initials: MR
authors.lastname: Tanas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D060787:Neoplasm Grading; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011166:Porphyrins / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D034741:RNA, Small Interfering; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D000091262:TEA Domain Transcription Factors; D046888:Tissue Array Analysis; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D000077362:Verteporfin; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C526317:CCN2 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D015513:Oncogene Proteins; D010750:Phosphoproteins; D011166:Porphyrins; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000077362:Verteporfin; D055513:Connective Tissue Growth Factor; D017346:Protein Serine-Threonine Kinases
keywords: Hippo pathway; Pathology Section; TAZ; WWTR1; YAP; sarcoma