TAZ and YAP are frequently activated oncoproteins in sarcomas

Colleen A Fullenkamp; Sarah L Hall; Omar I Jaber; Brittany L Pakalniskis; Erica C Savage; Johanna M Savage; Georgina K Ofori-Amanfo; Allyn M Lambertz; Stephanie D Ivins; Christopher S Stipp; Benjamin J Miller; Mohammed M Milhem; Munir R Tanas

doi:10.18632/oncotarget.8979

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TAZ and YAP are frequently activated oncoproteins in sarcomas

Journal article

Open access

Peer reviewed

TAZ and YAP are frequently activated oncoproteins in sarcomas

Colleen A Fullenkamp, Sarah L Hall, Omar I Jaber, Brittany L Pakalniskis, Erica C Savage, Johanna M Savage, Georgina K Ofori-Amanfo, Allyn M Lambertz, Stephanie D Ivins, Christopher S Stipp, …

Oncotarget, Vol.7(21), pp.30094-30108

05/24/2016

DOI: 10.18632/oncotarget.8979

PMCID: PMC5058666

PMID: 27129148

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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.

Immunohistochemistry

Oncogene Proteins - genetics

Tissue Array Analysis

Humans

Protein-Serine-Threonine Kinases

Antineoplastic Agents - therapeutic use

Intracellular Signaling Peptides and Proteins - metabolism

Phosphoproteins - metabolism

Carcinogenesis - metabolism

Gene Knockdown Techniques

DNA-Binding Proteins - metabolism

Cell Nucleus - metabolism

Neoplasm Grading

RNA Interference

Muscle Proteins - metabolism

Antineoplastic Agents - pharmacology

Intracellular Signaling Peptides and Proteins - genetics

Oncogene Proteins - metabolism

Phosphoproteins - genetics

Porphyrins - pharmacology

Sarcoma - drug therapy

Sarcoma - pathology

Disease Progression

Sarcoma - metabolism

Transcription Factors - metabolism

Signal Transduction - drug effects

Adaptor Proteins, Signal Transducing - genetics

Cell Line, Tumor

Cell Proliferation - drug effects

RNA, Small Interfering

Adaptor Proteins, Signal Transducing - metabolism

Connective Tissue Growth Factor - metabolism

Details

Title: Subtitle: TAZ and YAP are frequently activated oncoproteins in sarcomas
Creators: Colleen A Fullenkamp - Department of Pathology, University of Iowa, Iowa City, IA, USA
Sarah L Hall - Department of Pathology, University of Iowa, Iowa City, IA, USA
Omar I Jaber - Department of Pathology, University of Iowa, Iowa City, IA, USA
Brittany L Pakalniskis - Department of Pathology, University of Iowa, Iowa City, IA, USA
Erica C Savage - Department of Pathology, University of Iowa, Iowa City, IA, USA
Johanna M Savage - Department of Pathology, University of Iowa, Iowa City, IA, USA
Georgina K Ofori-Amanfo - Department of Pathology, University of Iowa, Iowa City, IA, USA
Allyn M Lambertz - Department of Pathology, University of Iowa, Iowa City, IA, USA
Stephanie D Ivins - Department of Pathology, University of Iowa, Iowa City, IA, USA
Christopher S Stipp - Department of Biology, University of Iowa, Iowa City, IA, USA
Benjamin J Miller - Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA, USA
Mohammed M Milhem - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Munir R Tanas - Department of Pathology, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Oncotarget, Vol.7(21), pp.30094-30108
DOI: 10.18632/oncotarget.8979
PMID: 27129148
PMCID: PMC5058666
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: United States
Grant note: P30 CA086862 / NCI NIH HHS
Language: English
Date published: 05/24/2016
Academic Unit: Molecular Physiology and Biophysics; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Orthopedics and Rehabilitation; Biology; Internal Medicine
Record Identifier: 9983992098202771

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