Molecular Targeting of ERKs/RSK2 Signaling Axis in Cancer Prevention.
10.15430/JCP.2015.20.3.165
- Author:
Sun Mi YOO
1
;
Sung Jun CHO
;
Yong Yeon CHO
Author Information
1. College of Pharmacy, The Catholic University of Korea, Bucheon, Korea. yongyeong@catholic.ac.kr
- Publication Type:Review
- Keywords:
Carcinogenesis;
Neoplastic cell transformation;
Molecular targeting;
ERKs/RSK2 signaling;
Natural compounds
- MeSH:
Axis, Cervical Vertebra*;
Carcinogenesis;
Cell Cycle;
Cell Proliferation;
Cell Transformation, Neoplastic;
Chemoprevention;
Epigenomics;
Homeostasis;
Humans;
Intercellular Signaling Peptides and Proteins;
Phosphotransferases;
Skin;
Skin Neoplasms
- From:Journal of Cancer Prevention
2015;20(3):165-171
- CountryRepublic of Korea
- Language:English
-
Abstract:
RSK2 is a downstream signaling protein of ERK1 and ERK2 and plays a key role in physiological homeostasis. For this reason, RSK2 is a highly conserved protein among the p90RSK family members. In its location in the signaling pathway, RSK2 is a kinase just upstream of transcription and epigenetic factors, and a few kinases involved in cell cycle regulation and protein synthesis. Moreover, activation of RSK2 by growth factors is directly involved in cell proliferation, anchorage-independent cell transformation and cancer development. Direct evidences regarding the etiological roles of RSK2 in cancer development in humans have been published by our research group illustrating that elevated total- and phospho-RSK2 protein levels mediated by ERK1 and ERK2 are higher in skin cancer tissues compared to normal skin tissues. Notably, it has been shown that RSK2 ectopic expression in JB6 Cl41 cells induces cell proliferation and anchorage-independent cell transformation. Importantly, knockdown of RSK2 suppresses Ras-mediated foci formation and anchorage-independent colony growth of cancer cells. Kaempferol is a one of the natural compounds showing selectivity in inhibiting RSK2 activity in epidermal growth factor-induced G1/S cell cycle transition and cell transformation. Thus, ERKs/RSK2 signaling axis is an important target signaling molecule in chemoprevention.
