Myosin regulatory light chain phosphorylation is associated with leiomyosarcoma development
Myosin regulatory light chain phosphorylation is associated with leiomyosarcoma development
复制标题
肌球蛋白调节轻链磷酸化与平滑肌肉瘤的发展相关。
DOI：
10.1016/j.biopha.2017.05.139
复制
发表时间：
2017-08-01
影响因子：
7.5
通讯作者：
Zha, Juan-Min
中科院分区：
文献类型：
--
作者：
Li, Hua-Shan;Lin, Qian;Zha, Juan-Min
平滑肌肉瘤是一种罕见的恶性平滑肌肿瘤，其难以预测。肌球蛋白 II 参与许多功能，包括细胞收缩、迁移和粘附。肌球蛋白轻链激酶 (MLCK) 对肌球蛋白调节轻链 (MLC) 的磷酸化决定了肌球蛋白 II 的活性。然而，MLC磷酸化是否参与平滑肌肉瘤的细胞增殖仍不清楚。在本研究中，我们旨在探讨 MLCK 依赖性 MLC 磷酸化在平滑肌肉瘤发展中的作用。我们发现平滑肌肉瘤中MLCK、磷酸化MLC和Ki67的表达显着高于平滑肌瘤和邻近正常平滑肌细胞。 MLCK 表达与磷酸化 MLC 水平显着相关。 Kaplan-Meier生存分析显示，与MLCK或磷酸化MLC低表达的患者相比，MLCK或磷酸化MLC高表达的患者总生存时间较短。体外研究揭示了 MLC 磷酸化与细胞增殖之间的因果关系，通过 Ki67 染色评估，磷酸化 MLC（T19D、S20D）的表达增加了细胞增殖。相反，MLCK 特异性抑制剂减少了细胞增殖。我们得出结论，MLCK、磷酸化 MLC 和 Ki67 在平滑肌肉瘤中过度表达。 MLCK 依赖性 MLC 磷酸化可能是平滑肌肉瘤高增殖状态的原因。 MLCK 和磷酸化 MLC 是平滑肌肉瘤的潜在预后指标。 (C) 2017 Elsevier Masson SAS。版权所有。
Leiomyosarcoma is a rare malignant smooth muscle tumor which can be very unpredictable. Myosin II is involved in many functions, including cell contraction, migration, and adhesion. The phosphorylation of myosin regulatory light chain (MLC) by myosin light chain kinase (MLCK) determines the activity of Myosin II. However, it is still unclear whether MLC phosphorylation is involved in cell proliferation in leiomyosarcoma. In this study, we aimed to explore the role of MLCK-dependent MLC phosphorylation in leiomyosarcoma development. We found that the expression of MLCK, phosphorylated MLC, and Ki67 in leiomyosarcoma was significantly higher than in leiomyoma and adjacent normal smooth muscle cells. MLCK expression was significantly correlated with phosphorylated MLC level. Kaplan-Meier survival analysis revealed that patients with high expression of MLCK or phosphorylated MLC had shorter overall survival times compared with the patients with low expression of MLCK or phosphorylated MLC. In vitro studies revealed a causative link between MLC phosphorylation and cellular proliferation as expression of phosphomimetic MLC (T19D, S20D) increased cellular proliferation as assessed by Ki67 staining. In contrast, MLCK specific inhibitor reduced cellular proliferation. We concluded that MLCK, phosphorylated MLC and Ki67 were overexpressed in leiomyosarcoma. MLCK dependent MLC phosphorylation might be responsible for the high proliferative state in leiomyosarcoma. MLCK and phosphorylated MLC are potential prognostic indicators of leiomyosarcoma. (C) 2017 Elsevier Masson SAS. All rights reserved.