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J Clin Exp Tox 2017 | Volume 1 | Issue 2
Toxicology and Pharmacology
November 01-02, 2017 | Toronto, Canada
International Conference on
Molecular targeting of ERKs-RSK2 signaling axis in human cancer
Yong-Yeon Cho and Cheol-Jung Lee
The Catholic University of Korea, Korea
Receptor tyrosine kinases (RTKs) which are activated by diverse
stimuli, such as growth factors, cytokines and environmental
stresses, play a key role in cell proliferation, transformation
and cancer development in humans. Since constitutive active
mutations in Ras and Raf are frequently observed with high
percentage in many solid tumors, including colon, pancreas,
ovarian, melanoma, non-small cell lung and other cancers,
Ras-mediated Rafs/MEK/ERKs/RSK2 signaling axis plays a key
role in the regulation of cell proliferation, transformation and
cancer development. Thus, Ras/Rafs/MEKs/ERKs/RSKs signaling
pathway has become an important target to develop/identify
chemopreventive and therapeutic agents. Recently, our results
demonstrated that RSK2, a downstream kinase of ERKs, is an
important proof-of-concept on the human cancer development.
Ectopic expression of RSK2 induced anchorage-independent
cell transformation without stimulation of tumor promoters
such as epidermal growth factor. Moreover, human skin cancer
tissue array demonstrated that total- and phospho-RSK2 protein
levels were higher in skin cancer tissues compared with normal
skin tissues. Utilizing cutting edge molecular and computational
research tools, we provided evidences that kaempferol and
eriodictyol were natural compounds which target and inhibit
RSK2 activity. Moreover, we found that magnolin, a natural
compound abundantly found in magnolia flos, targeted ERK1
and ERK2 and inhibited ERK1 and ERK2’s activities with 68 nM
and 16.5 nM of IC50 values. Moreover, magnolin suppressed cell
migration and invasion in cancer cells by inhibition of epithelial-
to-mesenchymal transition of cancer cells. Taken together, our
results provide strong evidences that ERKs and RSK2 are key
kinases regulating cell proliferation and transformation, and
are important targets to develop/identify small molecules as
chemopreventive and/or therapeutic agents.
Speaker Biography
Yong-Yeon Cho, PhD, is an Associate Professor and Director for Integrated Research
Institute of Pharmacutical Sciences at the College of Pharmacy, The Catholic University
of Korea. He earned his PhD degree at the Tohoku University (Applied Genetic
Engineering) under the supervision of Professor Tokuo T Yamamoto in Sendai, Japan
in 2000. He then joined Zigang Dong as a Post-Doc at the Hormel Institute, University
of Minnesota, in Dec-2001. He brought with him his expertise in Molecular Biology
and Genetic Engineering, which was integral to the research of protein-protein
interactions, signaling networks and molecular targeting of small molecules. Based
on his scientific achievements, he became Research Assistant Professor at the Hormel
Institute, University of Minnesota in 2005. His efforts resulted in the breakthrough
that the post-translational modification of stem cell factors plays an important role to
regulate stemness of ES cells and reprogramming efficiency. He came back and started
a new endeavor in Korea in 2011. Currently, he continues his research on molecular
mechanisms of novel signaling pathways regulating protein stability regulation in
cancer development and chemoresistance.
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