Kamikawa Yohei, Yokota Kento, Oikawa Kosuke, Sato Fuyuki, Muragaki Yasuteru
Department of Pathology, Wakayama Medical University, Wakayama 641-8509, Japan.
Oncol Lett. 2020 Dec;20(6):369. doi: 10.3892/ol.2020.12232. Epub 2020 Oct 19.
Myxoid liposarcoma (MLS) is thought to occur due to defective adipocytic differentiation in mesenchymal stem cells. A promising strategy for MLS treatment is the prevention of sarcomagenesis by promoting the terminal differentiation of MLS cells into adipocytes. Previous studies have reported that the suppression of megakaryoblastic leukemia 1 (MKL1) expression induces adipocytic differentiation in preadipocyte cell lines. The present study aimed to investigate the effects of MKL1 suppression on MLS cells. In the present study, MKL1 knockdown was demonstrated to promote the adipocytic differentiation of an MLS-derived cell line, designated 1955/91, under adipogenic conditions. This suggests that therapeutic targeting of the MKL1-associated molecular pathway has potential as a promising method of MLS treatment. However, the induction of adipogenesis by MKL knockdown was incomplete, and Oil Red O staining indicated that intracellular lipid droplets were only sporadically generated. Conversely, MKL1 knockdown reduced the growth of the MLS cells. As adipocytic differentiation requires cellular confluence, the decreased growth rate of the MLS cells following MKL1 knockdown could be attributed to the incomplete induction of adipogenesis. Translocated in liposarcoma-CCAAT/enhancer-binding protein homologous protein (TLS-CHOP) is an MLS-specific oncoprotein that is thought to play key roles in sarcomagenesis and the suppression of adipocytic differentiation. However, the results of western blotting analyses suggest that TLS-CHOP has limited effects on MKL1 expression in MLS cells and that MKL1 knockdown hardly affects TLS-CHOP expression. Thus, it is postulated that the inhibitory effect of TLS-CHOP on adipogenesis is not associated with MKL1 expression. However, MKL1 and the molecular pathway involving MKL1 appear to be attractive targets for the differentiation therapy of MLS.
黏液样脂肪肉瘤（MLS）被认为是由于间充质干细胞中脂肪细胞分化缺陷而发生的。MLS治疗的一个有前景的策略是通过促进MLS细胞向脂肪细胞的终末分化来预防肉瘤发生。先前的研究报道，巨核母细胞白血病1（MKL1）表达的抑制可诱导前脂肪细胞系中的脂肪细胞分化。本研究旨在探讨抑制MKL1对MLS细胞的影响。在本研究中，已证明在成脂条件下，敲低MKL1可促进一种源自MLS的细胞系（命名为1955/91）的脂肪细胞分化。这表明靶向MKL1相关分子途径进行治疗有潜力成为一种有前景的MLS治疗方法。然而，敲低MKL诱导的脂肪生成并不完全，油红O染色表明细胞内脂滴只是偶尔产生。相反，敲低MKL1可降低MLS细胞的生长。由于脂肪细胞分化需要细胞汇合，敲低MKL1后MLS细胞生长速率的降低可能归因于脂肪生成诱导不完全。脂肪肉瘤-CCAAT/增强子结合蛋白同源蛋白（TLS-CHOP）是一种MLS特异性癌蛋白，被认为在肉瘤发生和脂肪细胞分化抑制中起关键作用。然而，蛋白质印迹分析结果表明，TLS-CHOP对MLS细胞中MKL1表达的影响有限，敲低MKL1对TLS-CHOP表达几乎没有影响。因此，推测TLS-CHOP对脂肪生成的抑制作用与MKL1表达无关。然而，MKL1和涉及MKL1的分子途径似乎是MLS分化治疗的有吸引力的靶点。
