Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany.
EMBO Mol Med. 2019 May;11(5). doi: 10.15252/emmm.201910470.
Fused in sarcoma: DNA damage‐inducible transcript 3 protein (FUS:DDIT3) is a chimeric fusion oncoprotein present in 90% of human myxoid liposarcomas (MLS). The study by Trautmann in this issue of utilizes a drop‐out RNAi screen to establish hyperactive Yes‐associated protein 1 (YAP1), a major downstream nuclear effector of the Hippo signaling pathway, as a selectively essential transcript promoting viability and growth of MLS. These observations add to a growing body of evidence underscoring the importance of dysregulation of Hippo signaling in soft‐tissue sarcomas expressing fusion oncoproteins and identify a novel target for therapeutic intervention in MLS. Comprehensive molecular characterization pipelines are needed to screen patients with advanced soft‐tissue sarcomas for the presence of druggable alterations, including but not limited to nuclear YAP1 expression in MLS, to facilitate treatment decisions and advance therapy.
DNA 损伤诱导转录物 3 蛋白（FUS:DDIT3）是一种嵌合融合癌蛋白，存在于 90%的人类黏液样脂肪肉瘤（MLS）中。Trautmann 在本期杂志中的研究利用滴度 RNAi 筛选，确立了过度活跃的 Yes 相关蛋白 1（YAP1），作为 Hippo 信号通路的主要下游核效应物，是促进 MLS 活力和生长的选择性必需转录物。这些观察结果增加了越来越多的证据，强调了在表达融合癌蛋白的软组织肉瘤中 Hippo 信号失调的重要性，并确定了 MLS 治疗干预的新靶点。需要全面的分子特征分析管道来筛查晚期软组织肉瘤患者是否存在可用药的改变，包括但不限于 MLS 中的核 YAP1 表达，以促进治疗决策和推进治疗。
