Wu Tianhui, Chen Ziming, Liu Xin, Wu Xinyan, Wang Zhaobo, Guo Weiqiang
School of Chemistry and Life Science, Suzhou University of Science and Technology, Suzhou, China.
Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
Anticancer Agents Med Chem. 2025;25(1):35-41. doi: 10.2174/0118715206329546240830055233.
P90 ribosomal S6 kinase 2 (RSK2) is an important member of the RSK family, functioning as a kinase enzyme that targets serine and threonine residues and contributes to regulating cell growth. RSK2 comprises two major functional domains: the N-terminal kinase domain (NTKD) and the C-terminal kinase domain (CTKD). RSK2 is situated at the lower end of the Mitogen-activated protein kinases (MAPK) signaling pathway and is phosphorylated by the direct regulation of Extracellular signal-regulating kinase (ERK). RSK2 has been found to play a pivotal role in regulating cell proliferation, apoptosis, metastasis, and invasion in various cancer cells, including breast cancer and melanoma. Consequently, RSK2 has emerged as a potential target for the development of anti-cancer drugs. Presently, several inhibitors are undergoing clinical trials, such as SL0101. Current inhibitors of RSK2 mainly bind to its NTK or CTK domains and inhibit their activity. Natural products serve as an important resource for drug development and screening and with the potential to identify RSK2 inhibitors. This article discusses how RSK2 influences tumor cell proliferation, prevents apoptosis, arrests the cell cycle process, and promotes cancer metastasis through its regulation of downstream pathways or interaction with other biological molecules. Additionally, the paper also covers recent research progress on RSK2 inhibitors and the mechanisms of action of natural RSK2 inhibitors on tumors. This review emphasizes the significance of RSK2 as a potential therapeutic target in cancer and offers a theoretical basis for the clinical application of RSK2 inhibitors.
p90核糖体S6激酶2（RSK2）是RSK家族的重要成员，作为一种激酶，作用于丝氨酸和苏氨酸残基，有助于调节细胞生长。RSK2包含两个主要功能域：N端激酶结构域（NTKD）和C端激酶结构域（CTKD）。RSK2位于丝裂原活化蛋白激酶（MAPK）信号通路的下游，通过细胞外信号调节激酶（ERK）的直接调控而被磷酸化。已发现RSK2在调节包括乳腺癌和黑色素瘤在内的多种癌细胞的增殖、凋亡、转移和侵袭中起关键作用。因此，RSK2已成为抗癌药物开发的潜在靶点。目前，有几种抑制剂正在进行临床试验，如SL0101。目前的RSK2抑制剂主要与其NTK或CTK结构域结合并抑制其活性。天然产物是药物开发和筛选的重要资源，具有鉴定RSK2抑制剂的潜力。本文讨论了RSK2如何通过调节下游通路或与其他生物分子相互作用来影响肿瘤细胞增殖、阻止细胞凋亡、阻断细胞周期进程以及促进癌症转移。此外，本文还介绍了RSK2抑制剂的最新研究进展以及天然RSK2抑制剂对肿瘤的作用机制。这篇综述强调了RSK2作为癌症潜在治疗靶点的重要性，并为RSK2抑制剂的临床应用提供了理论依据。
