論文 - 詳細
| RRC ID | 78428 |
|---|---|
| 著者 | Takihira S, Yamada D, Osone T, Takao T, Sakaguchi M, Hakozaki M, Itano T, Nakata E, Fujiwara T, Kunisada T, Ozaki T, Takarada T. |
| タイトル | PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours. |
| ジャーナル | Br J Cancer |
| 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. |
| 公開日 | 2024-3-6 |
| DOI | 10.1038/s41416-024-02632-8 |
| PII | 10.1038/s41416-024-02632-8 |
| PMID | 38448751 |
| PMC | PMC11058259 |
| MeSH | Animals Cell Line, Tumor DNA Topoisomerases, Type II* / genetics DNA Topoisomerases, Type II* / metabolism Epithelial-Mesenchymal Transition* Gene Expression Regulation, Neoplastic Homeodomain Proteins* / genetics Homeodomain Proteins* / metabolism Humans Mice Nerve Sheath Neoplasms / genetics Nerve Sheath Neoplasms / metabolism Nerve Sheath Neoplasms / pathology Poly-ADP-Ribose Binding Proteins* / genetics Poly-ADP-Ribose Binding Proteins* / metabolism Prognosis Signal Transduction |
| IF | 5.791 |
| リソース情報 | |
| ヒト・動物細胞 | HS-PSS(RCB2362) HS-Sch-2(RCB2230) MRC-5 |