TAZ and YAP are frequently activated oncoproteins in sarcomas
| Autor: | Benjamin J. Miller, Georgina K. Ofori-Amanfo, Mohammed M. Milhem, Johanna Savage, Colleen Fullenkamp, Erica C. Savage, Munir R. Tanas, Christopher S. Stipp, Stephanie D. Ivins, Omar I. Jaber, Brittany L. Pakalniskis, Sarah L. Hall, Allyn M. Lambertz |
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| Rok vydání: | 2016 |
| Předmět: |
TAZ
0301 basic medicine Pathology sarcoma Carcinogenesis Hippo pathway Muscle Proteins WWTR1 medicine.disease_cause RNA Small Interfering Oncogene Proteins YAP1 Chemistry Intracellular Signaling Peptides and Proteins TEA Domain Transcription Factors Immunohistochemistry DNA-Binding Proteins Oncology Gene Knockdown Techniques Disease Progression RNA Interference YAP Sarcoma Signal Transduction medicine.medical_specialty Porphyrins Antineoplastic Agents Protein Serine-Threonine Kinases Liposarcoma Undifferentiated Pleomorphic Sarcoma 03 medical and health sciences Cell Line Tumor Pathology Section medicine Humans Adaptor Proteins Signal Transducing Cell Proliferation Cell Nucleus Hippo signaling pathway Connective Tissue Growth Factor Verteporfin YAP-Signaling Proteins Phosphoproteins medicine.disease Research Paper: Pathology 030104 developmental biology Tissue Array Analysis Tumor progression Transcriptional Coactivator with PDZ-Binding Motif Proteins Trans-Activators Cancer research Neoplasm Grading Transcription Factors |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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