Cited by 103Hippo pathway signaling and YAP/TAZSarcoma Diagnosis and TreatmentCancer-related molecular mechanisms research

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Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis

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Eisinger-Mathason, T. S. Karin, Mucaj, Vera, Biju, Kevin M., Nakazawa, Michael S., Gohil, Mercy, Cash, Timothy P., Yoon, Sam S., Skuli, Nicolas, Park, Kyung Min, Gerecht, Sharon, Simon, M. Celeste·2015·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1420005112PMC PMC4491775

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Abstract

Genetic aberrations responsible for soft-tissue sarcoma formation in adults are largely unknown, with targeted therapies sorely needed for this complex and heterogeneous family of diseases. Here we report that that the Hippo pathway is deregulated in many soft-tissue sarcomas, resulting in elevated expression of the effector molecule Yes-Associated Protein (YAP). Based on data gathered from human sarcoma patients, a novel autochthonous mouse model, and mechanistic analyses, we determined that YAP-dependent expression of the transcription factor forkhead box M1 (FOXM1) is necessary for cell proliferation/tumorigenesis in a subset of soft-tissue sarcomas. Notably, FOXM1 directly interacts with the YAP transcriptional complex via TEAD1, resulting in coregulation of numerous critical pro-proliferation targets that enhance sarcoma progression. Finally, pharmacologic inhibition of FOXM1 decreases tumor size in vivo, making FOXM1 an attractive therapeutic target for the treatment of some sarcoma subtypes.

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Additional file 1 of Co-expression of YAP and TAZ associates with chromosomal instability in human cholangiocarcinoma
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Additional file 3 of Co-expression of YAP and TAZ associates with chromosomal instability in human cholangiocarcinoma
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Authors: Eisinger-Mathason, T. S. K., Mucaj, V., Biju, K. M., Nakazawa, M. S., Gohil, M., Cash, T. P., Yoon, S. S., Skuli, N., Park, K. M., Gerecht, S., & Simon, M. C.
Affiliations: Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104;
University of Pennsylvania (US)
Memorial Sloan Kettering Cancer Center (US)
Inserm (FR)
Johns Hopkins University (US)
Howard Hughes Medical Institute (US)
ORCID: Mucaj, Vera
Biju, Kevin M.
Nakazawa, Michael S.
Gohil, Mercy
Yoon, Sam S.
Skuli, Nicolas
Park, Kyung Min
Gerecht, Sharon
Simon, M. Celeste
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2015-06-15
Volume: 112
Issue: 26
Pages: E3402-11
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1420005112
PMC: PMC4491775
OpenAlex: W1633738151
Cited by: 103
References: 51
Citations by year: 2026: 1 · 2025: 4 · 2024: 7 · 2023: 5 · 2022: 12 · 2021: 22 · 2020: 10 · 2019: 9 · 2018: 10 · 2017: 8 · 2016: 12 · 2015: 3
FWCI: 5.86
Type: journal article
Language: en
Update notices: correction (2024-01-03)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.pnas.org/site/misc/userlicense.xhtml (vor, 183 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: HHS | NIH | National Cancer Institute (F32 CA156979-01, T32 CA009140-36, F31 CA174211-01, R01 CA138265)
HHS | National Institutes of Health (U54CA143868)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords: soft tissue sarcoma, Hippo signaling pathway, YAP, FOXM1, TEAD1, carcinogenesis, cell proliferation, transcriptional co-regulation, autochthonous mouse model, pharmacological inhibition, therapeutic target
MeSH terms: Forkhead Box Protein M1, Hippo Signaling Pathway, YAP-Signaling Proteins, Humans, Phosphoproteins, Sarcoma, Transcription Factors, Protein Serine-Threonine Kinases, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation, Forkhead Transcription Factors, Carcinogenesis

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Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis

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