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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
Inhibition of ERKs/RSK2/IκBα signaling axis by magnolin suppresses cancer cell invasion and migration
Sun-Mi Yoo, Cheol-Jung Lee, Sueng-Min Kim, Seon-Yeon Cho
and
Yong-Yeon Cho
The Catholic University of Korea, Korea
P
reviously, our study demonstrated that IκBα phosphorylation at
Ser32 by RSK2, a kinase regulated their activity by ERK1 and 2,
induced NF-κB transactivation activity through IκBα destabilization,
and magnolin inhibited ERK1 and 2 activities by targeting of the
ERK active pocket. However, the role of magnolin in cell migration
has not been clearly elucidated. Here, we found that magnolin
inhibited NF-κB transactivation activity by suppression of ERK1/2/
RSK2 signaling pathway. We demonstrated that magnolin abrogated
increase of EGF-induced COX-2 protein level and wound healing in a
dose dependent manner. In human lung cancer cells such as A549
and H1975 which harbor constitutive active Ras and EGFR mutants,
respectively, we found that magnolin suppressed wound healing
and cell invasion in Boyden chamber assay in a dose dependent
manner. Importantly, gene expressions and activities of MMP-2
and -9 were inhibited by magnolin treatment. Notably, E-cadherin
levels, an epithelial marker, was elevated by magnolin treatment
and N-cadherin, Snail, Vimentin levels, mesenchymal markers, were
suppressed by magnolin treatment in a dose dependent manner. In
addition, the knockdown or knockout of RSK2 in A549 lung cancer
cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling
suppressed epithelial-mesenchymal transition. These results
demonstrated that magnolin is beneficial for the anti-invasion and
-migration in cancer metastasis.
Speaker Biography
Sun-Mi Yoo is an Ph. D. course sudent at the College of Pharrmacy, The Catholic
University of Korea. Ms Yoo graduated B. S. degree at the Yonsei University (Life science)
and entered graduate school of M. S./Ph. D. joint program on major of Pharmecutical
Biochemistry in 2014 supervised by professor Yong-Yeon Cho. Ms. Yoo has studied on
the protein-protein interaction and signaling network involved in cell transformation,
cancer metastasis anc chemoresistance. Ms. Yoo found that ERKs/RSK2 signaling
pathway plays a key role in cancer cell metastasis and molecular targeting of ERKs using
magnolin, a natural compound abendently found in magnolia flos, strongly suppressed
cancer cell migration and invasion. Moreover, During the M. S./Ph. D. course, she has
identified a novel signaling pathway involved in chemoresistance through p90RSKs.
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