淋巴样增强因子1（LEF1）可减少横纹肌肉瘤的肿瘤进展，并在一部分横纹肌肉瘤中诱导肌分化。
LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma.
作者信息
Dräger Julia, Simon-Keller Katja, Pukrop Tobias, Klemm Florian, Wilting Jörg, Sticht Carsten, Dittmann Kai, Schulz Matthias, Leuschner Ivo, Marx Alexander, Hahn Heidi
机构信息
Department of Human Genetics, University Medical Center, Göttingen 37073, Germany.
Institute of Pathology, University Medical Center Mannheim, Mannheim 68167, Germany.
出版信息
Oncotarget. 2017 Jan 10;8(2):3259-3273. doi: 10.18632/oncotarget.13887.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness especially of ARMS cells. LEF1 knockdown experiments in cell lines reveal that depending on the cellular context, LEF1 can induce pro-apoptotic signals. LEF1 can also suppress proliferation, migration and invasiveness of RMS cells both in vitro and in vivo. Furthermore, LEF1 can induce myodifferentiation of the tumor cells. This may involve regulation of other LEF1/TCF factors i.e. TCF1, whereas β-catenin activity plays a subordinate role. Together these data suggest that LEF1 rather has tumor suppressive functions and attenuates aggressiveness in a subset of RMS.
横纹肌肉瘤（RMS）是儿童中最常见的软组织肉瘤，具有骨骼肌分化特征。儿童RMS的两种主要亚型是肺泡型（ARMS）和胚胎型RMS（ERMS）。我们证明，与正常骨骼肌相比，约50%的ARMS和ERMS过表达LEF1/TCF转录因子LEF1，并且LEF1可以抑制尤其是ARMS细胞的侵袭性。细胞系中的LEF1敲低实验表明，根据细胞环境的不同，LEF1可以诱导促凋亡信号。LEF1还可以在体外和体内抑制RMS细胞的增殖、迁移和侵袭。此外，LEF1可以诱导肿瘤细胞的肌分化。这可能涉及对其他LEF1/TCF因子（即TCF1）的调节，而β-连环蛋白活性起次要作用。这些数据共同表明，LEF1更具有肿瘤抑制功能，并减弱了一部分RMS的侵袭性。
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