Research Papers: Pathology:
TAZ and YAP are frequently activated oncoproteins in sarcomas
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Colleen A. Fullenkamp1, Sarah L. Hall1, Omar I. Jaber1, Brittany L. Pakalniskis1, Erica C. Savage1, Johanna M. Savage1, Georgina K. Ofori-Amanfo1, Allyn M. Lambertz1, Stephanie D. Ivins1, Christopher S. Stipp2, Benjamin J. Miller3, Mohammed M. Milhem4 and Munir R. Tanas1
1 Department of Pathology, University of Iowa, Iowa City, IA, USA
2 Department of Biology, University of Iowa, Iowa City, IA, USA
3 Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA, USA
4 Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Munir R. Tanas, email:
Keywords: TAZ, WWTR1, YAP, Hippo pathway, sarcoma, Pathology Section
Received: February 03, 2016 Accepted: April 09, 2016 Published: April 25, 2016
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.
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