American Association for Cancer Research
15357163mct180763-sup-205015_2_supp_5261480_pkys7m.pdf (258.92 kB)

Supplementary Figure S1 from Phosphatidylinositol-3-kinase (PI3K)/Akt Signaling is Functionally Essential in Myxoid Liposarcoma

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journal contribution
posted on 2023-04-03, 15:04 authored by Marcel Trautmann, Magdalene Cyra, Ilka Isfort, Birte Jeiler, Arne Krüger, Inga Grünewald, Konrad Steinestel, Bianca Altvater, Claudia Rossig, Susanne Hafner, Thomas Simmet, Jessica Becker, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann

Supplementary Figure S1: In vitro and in vivo evaluation of PI3K suppression (LY294002) in myxoid liposarcoma cell lines.


Deutsche Forschungsgemeinschaft


University of Münster Medical School



Myxoid liposarcoma (MLS) is an aggressive soft-tissue tumor characterized by a specific reciprocal t(12;16) translocation resulting in expression of the chimeric FUS–DDIT3 fusion protein, an oncogenic transcription factor. Similar to other translocation-associated sarcomas, MLS is characterized by a low frequency of somatic mutations, albeit a subset of MLS has previously been shown to be associated with activating PIK3CA mutations. This study was performed to assess the prevalence of PI3K/Akt signaling alterations in MLS and the potential of PI3K-directed therapeutic concepts. In a large cohort of MLS, key components of the PI3K/Akt signaling cascade were evaluated by next generation seqeuncing (NGS), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). In three MLS cell lines, PI3K activity was inhibited by RNAi and the small-molecule PI3K inhibitor BKM120 (buparlisib) in vitro. An MLS cell line–based avian chorioallantoic membrane model was applied for in vivo confirmation. In total, 26.8% of MLS cases displayed activating alterations in PI3K/Akt signaling components, with PIK3CA gain-of-function mutations representing the most prevalent finding (14.2%). IHC suggested PI3K/Akt activation in a far larger subgroup of MLS, implying alternative mechanisms of pathway activation. PI3K-directed therapeutic interference showed that MLS cell proliferation and viability significantly depended on PI3K-mediated signals in vitro and in vivo. Our preclinical study underlines the elementary role of PI3K/Akt signals in MLS tumorigenesis and provides a molecularly based rationale for a PI3K-targeted therapeutic approach which may be particularly effective in the subgroup of tumors carrying activating genetic alterations in PI3K/Akt signaling components.