A rising cancer prevention target of RSK2 in human skin cancer

Frontiers in Oncology

Yong-Yeon eCho¹  Arul eNarayanasamy¹ 

[1] College of Pharmacy, The Catholic University of Korea;

关键词: Chemoprevention;    Carcinogenesis;    Skin Cancer;    Rsk2;    RSK2 inhibitors;   

DOI  :  10.3389/fonc.2013.00201

来源: DOAJ

【 摘 要 】

RSK2 is a p90 ribosomal S6 kinase family (p90RSK) member regulating cell proliferation and transformation induced by tumor promoters such as epithelial growth factor (EGF) and 12-O-tetradecanoylphorbol 13-acetate (TPA). This family of p90RSK has classified as a serine/threonine kinase that respond to many growth factors, peptide hormones, neurotransmitters, and environmental stresses such as ultraviolet light (UV). Our recent study demonstrates that RSK2 plays a key role in human skin cancer development. Activation of RSK2 by EGF and UV through ERKs 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 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 malignant melanoma. Kaempferol and eriodictyol are natural substances to inhibit kinase activity of the RSK2 N-terminal kinase domain, which is a critical kinase domain to transducer 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.

【 授权许可】

Unknown