RSK in tumorigenesis: Connections to steroid signaling

• Published in: Steroids Vol. 75; no. 3; pp. 191 - 202
• Main Authors: Eisinger-Mathason, T.S. Karin, Andrade, Josefa, Lannigan, Deborah A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01.03.2010; Elsevier
• Subjects: Androgen receptor; Biological and medical sciences; Cell Proliferation; Cell Transformation, Neoplastic; Cyclin D1 - genetics; Cyclin D1 - metabolism; Enzyme Activation; Estrogen receptor; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; MAPK pathway; Neoplasms - enzymology; Neoplasms - pathology; p90 ribosomal S6 kinase; Ribosomal Protein S6 Kinases - genetics; Ribosomal Protein S6 Kinases - metabolism; Signal Transduction - physiology; Steroids - metabolism; Tumorigenesis; Vertebrates: endocrinology; MAPK pathway; Estrogen receptor; Tumorigenesis; p90 ribosomal S6 kinase; Androgen receptor; Steroid; Signal transduction; Enzyme; Transferases; Mitogen-activated protein kinase
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2009.12.010

The Ser/Thr kinase family, RSK, has been implicated in numerous types of hormone-dependent and -independent cancers. However, there has been little consideration of RSKs as downstream mediators of steroid hormone non-genomic effects or of their ability to facilitate steroid receptor-mediated gene expression. Steroid hormone signaling can directly stimulate the MEK/ERK/RSK pathway to regulate cellular proliferation and survival in transformed cells. To date, multiple mechanisms of RSK and steroid hormone receptor-mediated proliferation/survival have been elucidated. For example, RSK enhances proliferation of breast and prostate cancer cells via its ability to control the levels of the estrogen receptor co-activator, cyclin D1. While in lung and other tumors RSK may control apoptosis via estrogen-mediated regulation of mitochondrial integrity. Thus the RSKs could be important anti-cancer therapeutic targets in many different transformed tissues. The recent discovery of RSK-specific inhibitors will advance our current understanding of RSK in transformation and drive these studies into animal and clinical models. In this review we explore the mechanisms associated with RSK in tumorigenesis and their relationship to steroid hormone signaling.