Huang Yongxiu, Peng Meixi, Qin Huanhuan, Li Yan, Pei Li, Liu Xindong, Zhao Xueya
School of Medicine, Chongqing University, Chongqing 400044, China; Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Biology Science Institutes, Chongqing Medical University, Chongqing 400016, China.
Cell Signal. 2023 Jun;106:110623. doi: 10.1016/j.cellsig.2023.110623. Epub 2023 Feb 8.
Acute myeloid leukemia (AML) is a heterogeneous disorder with high morbidity and mortality under the existing treatment strategy. Here, we found that lysosome-associated protein transmembrane 4 beta (LAPTM4B) was frequently upregulated in AML, and high LAPTM4B was associated with poor outcome. Moreover, LAPTM4B promoted leukemia progression in vitro and in vivo. Mechanically, LAPTM4B interacted with RPS9, and positively regulated RPS9 protein stability, which enhanced leukemia cell progression via activating STAT3. Our findings indicate for the first time that LAPTM4B contributes to leukemia progression in a RPS9/STAT3-dependent manner, suggesting that LAPTM4B may serve as a promising target for treatment of AML.
急性髓系白血病(AML)是一种异质性疾病,在现有治疗策略下具有较高的发病率和死亡率。在此,我们发现溶酶体相关蛋白跨膜4β(LAPTM4B)在AML中经常上调,高LAPTM4B与不良预后相关。此外,LAPTM4B在体外和体内均促进白血病进展。机制上,LAPTM4B与核糖体蛋白S9(RPS9)相互作用,并正向调节RPS9蛋白稳定性,通过激活信号转导和转录激活因子3(STAT3)增强白血病细胞进展。我们的研究结果首次表明,LAPTM4B以RPS9/STAT3依赖的方式促进白血病进展,提示LAPTM4B可能是治疗AML的一个有前景的靶点。