Yes is a central mediator of cell growth in malignant mesothelioma cells
Yes is a central mediator of cell growth in malignant mesothelioma cells
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DOI：
10.3892/or.2012.2010
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发表时间：
2012-11-01
期刊：
影响因子：
4.2
通讯作者：
Yano, Tomohiro
中科院分区：
文献类型：
--
作者：
Sato, Ayami;Sekine, Miki;Yano, Tomohiro
Src 家族激酶 (SFK) 的组成型激活已被确定为恶性间皮瘤 (MM) 的不良预后因素，然而，导致恶性肿瘤的家族成员尚未确定。本研究旨在利用 RNA 干扰在各种 MM 细胞系中鉴定对细胞生长有贡献的 SFK 成员。在 MM 细胞中沉默 Yes 但不沉默 c-Src 或 Fyn 会导致细胞生长抑制。 Yes沉默引起的这种抑制作用主要依赖于G1细胞周期停滞，部分依赖于细胞凋亡的诱导。此外，敲除 Yes 会导致 β-连环蛋白信号失活，并随后降低细胞周期中 G1-S 转变所需的细胞周期蛋白 D 的水平。此外，与表达连环蛋白的其他 MM 细胞相比，Yes 敲除对缺乏 β-连环蛋白的 H28 MM 细胞的细胞生长抑制作用较小。总体而言，我们得出的结论是，Yes 是 MM 细胞生长的核心介质，不与 c-Src 等其他 SFK 共享。
The constitutive activation of the Src family kinases (SFKs) has been established as a poor prognostic factor in malignant mesothelioma (MM), however, the family member(s) which contribute to the malignancy have not been defined. This study aimed to identify the SFK member(s) contributing to cell growth using RNA interference in various MM cell lines. Silencing of Yes but not of c-Src or Fyn in MM cells leads to cell growth suppression. This suppressive effect caused by Yes silencing mainly depends on G1 cell cycle arrest and partly the induction of apoptosis. Also, the knockout of Yes induces the inactivation of beta-catenin signaling and subsequently decreases the levels of cyclin D necessary for G1-S transition in the cell cycle. In addition, Yes knockout has less effect on cell growth suppression in beta-catenin-deficient H28 MM cells compared to other MM cells which express the catenin. Overall, we conclude that Yes is a central mediator for MM cell growth that is not shared with other SFKs such as c-Src.