A novel ribosomal protein S6 kinase 2 inhibitor attenuates the malignant phenotype of cutaneous malignant melanoma cells by inducing cell cycle arrest and apoptosis.
A novel ribosomal protein S6 kinase 2 inhibitor attenuates the malignant phenotype of cutaneous malignant melanoma cells by inducing cell cycle arrest and apoptosis.
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DOI：
10.1080/21655979.2022.2080364
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发表时间：
2022-05
期刊：
影响因子：
4.9
通讯作者：
Peng, Cong
中科院分区：
文献类型：
--
作者：
Li, Yayun;Yu, Pian;Long, Jing;Tang, Ling;Zhang, Xu;Zhou, Zhe;Cao, DongSheng;Su, Juan;Chen, Xiang;Peng, Cong
恶性黑色素瘤（MM）是一种高度危及生命的肿瘤，导致大多数皮肤癌相关死亡。以前，核糖体蛋白S6激酶2（RSK 2），MAPK通路的下游效应子，代表了黑色素瘤的治疗靶点。AE 007被发现是一种靶向RSK 2抑制剂，随后的结果表明AE 007通过直接结合其蛋白激酶结构域来抑制RSK 2。AE 007导致细胞周期停滞和细胞凋亡，从而显著抑制黑色素瘤细胞的增殖、迁移和侵袭。然而，黑素细胞和角质形成细胞不受该化合物的影响。此外，RSK 2的抑制消除了AE 007对黑色素瘤细胞增殖的抑制作用。AE 007处理显著抑制Cyclin D1、Cyclin B1、CDK 2和Bcl-2的表达，同时增加PARP的裂解。此外，RNA测序结果表明，AE 007处理可以影响基因表达谱，包括细胞周期和DNA复制基因的表达。总之，AE 007是一种很有前途的以RSK 2为靶点的黑色素瘤治疗药物。
Malignant melanoma (MM) is a highly life-threatening tumor causing the majority of the cutaneous cancer-related deaths. Previously, ribosomal protein S6 kinase 2 (RSK2), the downstream effector of the MAPK pathway, represents a therapeutic target in melanoma. AE007 is discovered as a targeted RSK2 inhibitor, and subsequent results showed that AE007 inhibits RSK2 by directly binding to its protein kinase domain. AE007 causes cell cycle arrest and cellular apoptosis, thereby dramatically inhibiting proliferation, migration, and invasion of melanoma cells. Nevertheless, melanocytes and keratinocytes are not affected by this compound. In addition, suppression of RSK2 abrogates the inhibitory effect of AE007 on melanoma cell proliferation. AE007 treatment significantly inhibits the expression of Cyclin D1, Cyclin B1, CDK2, and Bcl-2, while raises the cleavage of PARP. Moreover, RNA sequencing results show that AE007 treatment can affect the genes expression profile, including the expression of cell cycle and DNA replication genes. In conclusion, AE007 is a promising melanoma therapeutic agent by targeting RSK2.
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影响因子：
5.8
作者：
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通讯作者：
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