College of Pharmacy, The Catholic University of Korea , Bucheon-si , Republic of Korea.
Front Oncol. 2013 Aug 5;3:201. doi: 10.3389/fonc.2013.00201. eCollection 2013.
RSK2 is a p90 ribosomal S6 kinase family (p90(RSK)) member regulating cell proliferation and transformation induced by tumor promoters such as epithelial growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate. This family of p90(RSK) has classified as a serine/threonine kinase that respond to many growth factors, peptide hormones, neurotransmitters, and environmental stresses such as ultraviolet (UV) light. Our recent study demonstrates that RSK2 plays a key role in human skin cancer development. Activation of RSK2 by EGF and UV through extracellular-activated protein kinases signaling pathway induces cell cycle progression, cell proliferation, and anchorage-independent cell transformation. Moreover, knockdown of RSK2 by si-RNA or sh-RNA abrogates cell proliferation and cell transformation of non-malignant human skin keratinocyte, and colony growth of malignant melanoma (MM) cells in soft agar. Importantly, activated and total RSK2 protein levels are highly detected in human skin cancer tissues including squamous cell carcinoma, basal-cell carcinoma, and MM. Kaempferol and eriodictyol are natural substances to inhibit kinase activity of the RSK2 N-terminal kinase domain, which is a critical kinase domain to transduce their activation signals to the substrates by phosphorylation. In this review, we discuss the role of RSK2 in skin cancer, particularly in activation of signaling pathways and potent natural substances to target RSK2 as chemopreventive and therapeutic agents.
RSK2 是 p90 核糖体 S6 激酶家族（p90(RSK)）的成员，可调节肿瘤促进剂（如表皮生长因子 (EGF) 和 12-O-十四烷酰佛波醇-13-醋酸酯）诱导的细胞增殖和转化。该 p90(RSK) 家族被归类为丝氨酸/苏氨酸激酶，可响应许多生长因子、肽激素、神经递质和环境应激物，如紫外线 (UV)。我们最近的研究表明，RSK2 在人类皮肤癌的发展中起着关键作用。EGF 和 UV 通过细胞外激活蛋白激酶信号通路激活 RSK2，可诱导细胞周期进程、细胞增殖和非依赖性细胞转化。此外，通过 si-RNA 或 sh-RNA 敲低 RSK2 可阻断非恶性人类皮肤角质形成细胞的增殖和转化，以及软琼脂中恶性黑色素瘤 (MM) 细胞的集落生长。重要的是，在包括鳞状细胞癌、基底细胞癌和 MM 在内的人类皮肤癌组织中高度检测到活化和总 RSK2 蛋白水平。山奈酚和圣草酚是抑制 RSK2 N 端激酶结构域激酶活性的天然物质，该激酶结构域是通过磷酸化将其激活信号转导至底物的关键激酶结构域。在这篇综述中，我们讨论了 RSK2 在皮肤癌中的作用，特别是在信号通路的激活和强效天然物质靶向 RSK2 作为化学预防和治疗剂方面的作用。
