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- Barkan, C., et al.
(författare)
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SPECIAL ISSUE ON HEAVY HAUL AND INNOVATIVE DEVELOPMENT
- 2010
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Ingår i: Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit. - 0954-4097 .- 2041-3017. ; 224:F5, s. I-II
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Tidskriftsartikel (refereegranskat)
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- Berthold, R., et al.
(författare)
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Fusion protein-driven IGF-IR/PI3K/AKT signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma
- 2022
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid liposarcoma (MLS) represents a common subtype of liposarcoma molecularly characterized by a recurrent chromosomal translocation that generates a chimeric FUS-DDIT3 fusion gene. The FUS-DDIT3 oncoprotein has been shown to be crucial in MLS pathogenesis. Acting as a transcriptional dysregulator, FUS-DDIT3 stimulates proliferation and interferes with adipogenic differentiation. As the fusion protein represents a therapeutically challenging target, a profound understanding of MLS biology is elementary to uncover FUS-DDIT3-dependent molecular vulnerabilities. Recently, a specific reliance on the Hippo pathway effector and transcriptional co-regulator YAP1 was detected in MLS; however, details on the molecular mechanism of FUS-DDIT3-dependent YAP1 activation, and YAP1 ' s precise mode of action remain unclear. In elaborate in vitro studies, employing RNA interference-based approaches, small-molecule inhibitors, and stimulation experiments with IGF-II, we show that FUS-DDIT3-driven IGF-IR/PI3K/AKT signaling promotes stability and nuclear accumulation of YAP1 via deregulation of the Hippo pathway. Co-immunoprecipitation and proximity ligation assays revealed nuclear co-localization of FUS-DDIT3 and YAP1/TEAD in FUS-DDIT3-expressing mesenchymal stem cells and MLS cell lines. Transcriptome sequencing of MLS cells demonstrated that FUS-DDIT3 and YAP1 co-regulate oncogenic gene signatures related to proliferation, cell cycle progression, apoptosis, and adipogenesis. In adipogenic differentiation assays, we show that YAP1 critically contributes to FUS-DDIT3-mediated adipogenic differentiation arrest. Taken together, our study provides mechanistic insights into a complex FUS-DDIT3-driven network involving IGF-IR/PI3K/AKT signals acting on Hippo/YAP1, and uncovers substantial cooperative effects of YAP1 and FUS-DDIT3 in the pathogenesis of MLS.
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- Rosenquist, R, et al.
(författare)
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Precision medicine in cancer: A paradigm shift
- 2022
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Ingår i: Seminars in cancer biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 84, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Tamborero, D, et al.
(författare)
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The Molecular Tumor Board Portal supports clinical decisions and automated reporting for precision oncology
- 2022
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Ingår i: Nature cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 251-
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing need for systems that efficiently support the work of medical teams at the precision-oncology point of care. Here, we present the implementation of the Molecular Tumor Board Portal (MTBP), an academic clinical decision support system developed under the umbrella of Cancer Core Europe that creates a unified legal, scientific and technological platform to share and harness next-generation sequencing data. Automating the interpretation and reporting of sequencing results decrease the need for time-consuming manual procedures that are prone to errors. The adoption of an expert-agreed process to systematically link tumor molecular profiles with clinical actions promotes consistent decision-making and structured data capture across the connected centers. The use of information-rich patient reports with interactive content facilitates collaborative discussion of complex cases during virtual molecular tumor board meetings. Overall, streamlined digital systems like the MTBP are crucial to better address the challenges brought by precision oncology and accelerate the use of emerging biomarkers.
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