Inhibition of Slug effectively targets leukemia stem cells via the Slc13a3/ROS signaling pathway.,Leukemia

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Inhibition of Slug effectively targets leukemia stem cells via the Slc13a3/ROS signaling pathway.
Leukemia ( IF 12.8 ) Pub Date : 2019-09-06 , DOI: 10.1038/s41375-019-0566-x
Zhonghui Zhang _{1,

2} , Lei Li ₃ , Chen Wu ₁ , Guoshu Yin _{2,

4} , Pei Zhu ₂ , Yalu Zhou ₂ , Yuanfan Hong ₂ , Hongyu Ni ₅ , Zhijian Qian ₆ , Wen-Shu Wu ₂

Affiliation

Leukemia stem cells (LSCs) are the rare populations of acute myeloid leukemia (AML) cells that are able to initiate, maintain, and propagate AML. Targeting LSCs is a promising approach for preventing AML relapse and improving long-term outcomes. While Slug, a zinc-finger transcription repressor, negatively regulates the self-renewal of normal hematopoietic stem cells, its functions in AML are still unknown. We report here that Slug promotes leukemogenesis and its loss impairs LSC self-renewal and delays leukemia progression. Mechanistically, Slc13a3, a direct target of Slug in LSCs, restricts the self-renewal of LSCs and markedly prolongs recipient survival. Genetic or pharmacological inhibition of SLUG or forced expression of Slc13a3 suppresses the growth of human AML cells. In conclusion, our studies demonstrate that Slug differentially regulates self-renewal of LSCs and normal HSCs, and both Slug and Slc13a3 are potential therapeutic targets of LSCs.

中文翻译：

通过Slc13a3 / ROS信号通路，抑制Slug可有效靶向白血病干细胞。

白血病干细胞（LSC）是少数能够启动，维持和传播AML的急性髓细胞白血病（AML）细胞。针对LSCs是预防AML复发和改善长期结果的一种有前途的方法。锌指转录阻遏物Slug负调节正常造血干细胞的自我更新，但其在AML中的功能仍然未知。我们在这里报告Slug促进白血病的发生，其损失损害了LSC的自我更新并延迟了白血病的进展。从机制上讲，Slc13a3是LSC中Slug的直接靶标，它会限制LSC的自我更新并显着延长受体的存活时间。对SLUG的遗传或药理抑制或Slc13a3的强制表达抑制了人AML细胞的生长。综上所述，

更新日期：2019-09-06

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