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http://dx.doi.org/10.15188/kjopp.2020.08.34.4.177

Anti-tumorigenic Effects of Angelica gigase Nakai Extract on MBA-MB-231 through Regulating Lats1/2 Activation  

Kim, Cho-Long (Department of Biomedical Sciences, Ajou University Graduate School of Medicine)
Kim, Nambin (Department of Biomedical Sciences, Ajou University Graduate School of Medicine)
Jeong, Han-Sol (Division of Applied Medicine, School of Korean Medicine, Pusan National University)
Shin, Yu-Su (Department of Ginseng and Medicinal Herb, National Institute of Horticultural and Herbal Science (NIHHS), Rural Development Administration (RDA))
Mo, Jung-Soon (Institute of Medical Science, Ajou University School of Medicine)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.34, no.4, 2020 , pp. 177-183 More about this Journal
Abstract
The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.
Keywords
Angelica gigas; YAP; LATS1/2; Hippo Pathway; Cancer;
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