Adjuvant Treatment For Patients With Malignant Peripheral Nerve Sheath Tumours

Kolberg, Matthias; Smeland, Sigbjørn; Lothe, and Ragnhild A

doi:10.4172/2167-7700.1000158

Chemotherapy (Los Angel)

2015

DOI: 10.4172/2167-7700.1000158

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Adjuvant Treatment For Patients With Malignant Peripheral Nerve Sheath Tumours

Matthias Kolberg¹,

Sigbjørn Smeland²,

and Ragnhild A Lothe³

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2024

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PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours

Takihira,

Yamada,

Osone

et al. 2024

Br J Cancer

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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.

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PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours

Takihira,

Yamada,

Osone

et al. 2024

Br J Cancer

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show abstract

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Adjuvant Treatment For Patients With Malignant Peripheral Nerve Sheath Tumours

Cited by 1 publication

References 22 publications

PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours

PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours

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