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Cited by 78Hippo pathway signaling and YAP/TAZSarcoma Diagnosis and TreatmentSignaling Pathways in Disease

TAZ and YAP are frequently activated oncoproteins in sarcomas

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Fullenkamp, Colleen A., Hall, Sarah L., Jaber, Omar I., Pakalniskis, Brittany L., Savage, Erica C., Savage, Johanna M., Ofori-Amanfo, Georgina K., Lambertz, Allyn M. +5 more·2016·Oncotarget
DOI 10.18632/oncotarget.8979PMC PMC5058666
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Abstract

// Colleen A. Fullenkamp 1 , Sarah L. Hall 1 , Omar I. Jaber 1 , Brittany L. Pakalniskis 1 , Erica C. Savage 1 , Johanna M. Savage 1 , Georgina K. Ofori-Amanfo 1 , Allyn M. Lambertz 1 , Stephanie D. Ivins 1 , Christopher S. Stipp 2 , Benjamin J. Miller 3 , Mohammed M. Milhem 4 and Munir R. Tanas 1 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 Correspondence to: 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 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.

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  • In DDLS, UPS, and MFS, the Hippo pathway is frequently deregulated through increased expression of the transcriptional coactivators YAP and TAZ.

    “In DDLS, UPS, and MFS, the Hippo pathway is frequently deregulated through increased expression of the transcriptional coactivators YAP and TAZ (9, 23–25).”

    From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [24]

    The Results section (page unavailable) reports frequent TAZ activation in myxofibrosarcoma (100%), dedifferentiated liposarcoma (100%), and undifferentiated pleomorphic sarcoma (82%). It describes these types as predominantly TAZ-activated, rather than showing frequent increased expression of both TAZ and YAP in all three. Increased expression of both is specifically shown for dedifferentiated versus well-differentiated liposarcoma. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • YAP and TAZ are paralogs that share similar functions and oncogenic activation in multiple tumor types, including breast and liver cancer and various soft tissue sarcomas including DDLS, MFS, and UPS.

    “The Hippo effectors YAP and TAZ are paralogs that share similar functions and oncogenic activation in multiple tumor types, including breast and liver cancer and various soft tissue sarcomas including DDLS, MFS, and UPS (9, 23, 24).”

    From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [24]

    The Introduction identifies YAP and TAZ as paralogs and describes them as oncoproteins in breast and liver cancers. The Results report activation in DDLS, MFS, and UPS, but predominantly of TAZ; the Discussion says YAP and TAZ are differentially activated and have different functions in vitro. The paper therefore does not support treating their functions and activation as uniformly similar across those sarcomas. Page numbers were not provided in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Prior studies show that Hippo pathway deregulation promotes tumorigenesis in WD/DDLS, MFS, and UPS through activation of YAP and TAZ.

    “This evidence supporting the importance of YAP and TAZ in driving WD/DDLS, MFS, and UPS is bolstered by prior studies showing that Hippo pathway deregulation promotes tumorigenesis in these sarcoma types through activation of YAP and TAZ (23, 24).”

    From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [24]

    The Results (page unavailable) report activated TAZ in myxofibrosarcoma, dedifferentiated liposarcoma, and undifferentiated pleomorphic sarcoma, but little activation in well-differentiated liposarcoma. The Discussion (page unavailable) says Hippo pathway inhibition is one suggested cause of YAP/TAZ activation, while other mechanisms are possible. The paper therefore supports YAP/TAZ involvement in these sarcomas, but not the claim that Hippo pathway deregulation drives tumorigenesis through both proteins in all three types. (LLM, conf=0.88)

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Research works printed but not linked: 45

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Authors
Fullenkamp, C. A., Hall, S. L., Jaber, O. I., Pakalniskis, B. L., Savage, E. C., Savage, J. M., Ofori-Amanfo, G. K., Lambertz, A. M., Ivins, S. D., Stipp, C. S., Miller, B. J., Milhem, M. M., & Tanas, M. R.
Affiliations
  • University of Iowa (US)
  • Department of Pathology, University of Iowa, Iowa City, IA, USA
Corresponding author
Tanas, Munir R.
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2016-04-25
Volume
7
Issue
21
Pages
30094-30108
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.8979
PMC
PMC5058666
OpenAlex
W2344198014
Cited by
78
References
43
Citations by year
2026: 4 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 12 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 2
FWCI
6.20
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
TAZ, YAP, Hippo signaling pathway, sarcoma, oncoprotein, nuclear localization, malignant fibrous histiocytoma, dedifferentiated liposarcoma, well-differentiated liposarcoma, conventional chondrosarcoma, tumor grade, verteporfin, connective tissue growth factor, soft agar colony formation, overall survival
MeSH terms
Verteporfin, YAP-Signaling Proteins, TEA Domain Transcription Factors, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Antineoplastic Agents, Cell Nucleus, DNA-Binding Proteins, Humans, Immunohistochemistry, Muscle Proteins, Phosphoproteins, Porphyrins, Sarcoma, Transcription Factors, Signal Transduction, Oncogene Proteins, Trans-Activators, Protein Serine-Threonine Kinases, Disease Progression, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Tissue Array Analysis, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Connective Tissue Growth Factor, Gene Knockdown Techniques, Neoplasm Grading, Carcinogenesis

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