ID | 66875 |
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Author |
Takihira, Shota
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamada, Daisuke
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Osone, Tatsunori
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takao, Tomoka
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sakaguchi, Masakiyo
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Hakozaki, Michiyuki
Department of Orthopedic Surgery, Fukushima Medical University School of Medicine
Itano, Takuto
Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nakata, Eiji
Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Fujiwara, Tomohiro
Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kunisada, Toshiyuki
Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Ozaki, Toshifumi
Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Takarada, Takeshi
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | Background: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated.
Methods: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. Results: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1–TOP2A interaction. Conclusion: Targeting the PRRX1–TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy. |
Note | The version of record of this article, first published in British Journal of Cancer, is available online at Publisher’s website: http://dx.doi.org/10.1038/s41416-024-02632-8
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Published Date | 2024-03-06
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Publication Title |
British Journal of Cancer
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Volume | volume130
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Issue | issue9
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Publisher | Springer Science and Business Media LLC
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Start Page | 1493
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End Page | 1504
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ISSN | 0007-0920
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NCID | AA00574355
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © The Author(s) 2024
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File Version | publisher
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DOI | |
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Related Url | isVersionOf https://doi.org/10.1038/s41416-024-02632-8
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License | http://creativecommons.org/licenses/by/4.0/
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Citation | Takihira, S., Yamada, D., Osone, T. et al. PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours. Br J Cancer 130, 1493–1504 (2024). https://doi.org/10.1038/s41416-024-02632-8
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Funder Name |
Japan Society for the Promotion of Science
Uehara Memorial Foundation
Takeda Science Foundation
Kobayashi Foundation for Cancer Research
Japan Agency for Medical Research and Development
Japan Science and Technology Agency
Okayama University
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助成番号 | 21K07178
21K07192
22K09401
202120121
2022045851
2022ER001
DNW-22022
23K14384
JPMJFR225H
|