Sökning: L773:2157 9024 >
Fusion protein-driv...
Fusion protein-driven IGF-IR/PI3K/AKT signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma
-
Berthold, R. (författare)
-
Isfort, I. (författare)
-
Erkut, C. (författare)
-
visa fler...
-
Heinst, L. (författare)
-
Grunewald, I. (författare)
-
Wardelmann, E. (författare)
-
Kindler, T. (författare)
-
- Åman, Pierre, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine
-
Grunewald, T. G. P. (författare)
-
Cidre-Aranaz, F. (författare)
-
Trautmann, M. (författare)
-
Frohling, S. (författare)
-
Scholl, C. (författare)
-
Hartmann, W. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2022-04-22
- 2022
- Engelska.
-
Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1
- Relaterad länk:
-
https://gup.ub.gu.se...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- chop
- expression
- target
- growth
- cells
- Oncology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Berthold, R.
-
Isfort, I.
-
Erkut, C.
-
Heinst, L.
-
Grunewald, I.
-
Wardelmann, E.
-
visa fler...
-
Kindler, T.
-
Åman, Pierre, 19 ...
-
Grunewald, T. G. ...
-
Cidre-Aranaz, F.
-
Trautmann, M.
-
Frohling, S.
-
Scholl, C.
-
Hartmann, W.
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Cancer och onkol ...
- Artiklar i publikationen
-
Oncogenesis
- Av lärosätet
-
Göteborgs universitet