Regulation and function of the RSK family in colorectal cancer

Abstract

P90 Ribosomal S6 Kinases (RSKs) constitute a class of Serine/Threonine (Ser/Thr) protein kinases and play a critical role as downstream targets in the Raf/MEK/ERK signaling pathway. Gaining insight into the biological function of RSK family proteins, given their functions in various tumors, is vital. The RSK family is involved in the regulation of cellular functions including cell proliferation, motility, invasion, and survival. The RSK family comprises four human isoforms (RSK1, RSK2, RSK3, and RSK4). The activation of RSK protein kinases is mediated through direct phosphorylation by extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphoinositide-dependent kinase 1 (PDK1) after the Ras/MAPK (mitogen-activated protein kinase) pathway is activated. Recent evidence suggests that RSK family proteins promote the onset and metastasis of cancer, leading to the association of the protein expression of these kinases with various cancer types, such as colorectal cancer (CRC), breast cancer, lung cancer, kidney cancer, leukemia, esophageal squamous cell carcinoma, ovarian cancer, glioma, and endometrial cancer. In this review, we summarize the latest research on the RSK family, focusing on its role in patients with CRC, along with associated treatment challenges and limitations. This information enhances our comprehension of the regulation and function of RSK family proteins, highlighting their potential as both clinical biomarkers for diagnosing CRC and targets for molecular therapeutic interventions in the future.