GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway.
GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway.
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DOI：
10.3389/fonc.2021.656608
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发表时间：
2021
影响因子：
4.7
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Li C;Li Z;Song L;Meng L;Xu G;Zhang H;Hu J;Li F;Liu C
自噬和凋亡是决定细胞命运的动态过程，调节这两个过程可以治疗癌症。GEFT在横纹肌肉瘤（rhabdomyosarcoma， RMS）中高表达，通过激活Rac1/Cdc42信号，加速RMS的致瘤性和转移，但其自噬和凋亡的调控机制尚不清楚。在我们的研究中，我们发现RMS组织与正常横纹肌组织相比，Rac1、Cdc42、mTOR、Bcl-2的表达水平较高，Beclin1、LC3、Bax的表达水平较低（P < 0.05）。此外，多因素分析证实Rac1是独立的预后因素（P < 0.05）， Beclin1蛋白的高表达水平与RMS患者的肿瘤直径密切相关（P = 0.044）， LC3蛋白的高表达水平与RMS患者的临床分期相关（P = 0.027）。此外，过表达GEFT可抑制RMS细胞的自噬和凋亡。加入Rac1/Cdc42抑制剂后，细胞自噬和凋亡的抑制作用减弱。Rac1和Cdc42可调控mTOR抑制RMS细胞自噬和凋亡。总之，这些研究表明GEFT-Rac1 / Cdc42-mTOR通路可以抑制RMS的自噬和凋亡，为创新治疗提供了证据。
Autophagy and apoptosis are dynamic processes that determine the fate of cells, and regulating these processes can treat cancer. GEFT is highly expressed in rhabdomyosarcoma (RMS), which accelerates the tumorigenicity and metastasis of RMS by activating Rac1/Cdc42 signaling, but the regulatory mechanisms of autophagy and apoptosis are unclear. In our study, we found that the RMS tissues had high Rac1, Cdc42, mTOR, and Bcl-2 expression levels and low Beclin1, LC3, and Bax expression levels compared with the normal striated muscle tissues (P < 0.05). In addition, multivariate analysis has proven that Rac1 is an independent prognostic factor (P < 0.05), and the high expression level of the Beclin1 protein was closely associated with the tumor diameter of the RMS patients (P = 0.044), whereas the high expression level of the LC3 protein was associated with the clinical stage of the RMS patients (P = 0.027). Furthermore, GEFT overexpression could inhibit autophagy and apoptosis in RMS. A Rac1/Cdc42 inhibitor was added, and the inhibition of autophagy and apoptosis decreased. Rac1 and Cdc42 could regulate mTOR to inhibit autophagy and apoptosis in RMS. Overall, these studies demonstrated that the GEFT–Rac1/Cdc42–mTOR pathway can inhibit autophagy and apoptosis in RMS and provide evidence for innovative treatments.
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影响因子：
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10.1124/jpet.113.207266
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