유방암세포에서 LATS1/2 활성에 의한 당귀 추출물의 항암효과

• Published in: 동의생리병리학회지 Vol. 34; no. 4; pp. 177 - 183
• Main Authors: 김초롱(Cho-Long Kim), 김남빈(Nambin Kim), 정한솔(Han-Sol Jeong), 신유수(Yu-Su Shin), 모정순(Jung-Soon Mo)
• Format: Journal Article
• Language: Korean
• Published: 한의병리학회 2020
• Subjects: 한의학; YAP; LATS1/2; Angelica gigas; Hippo Pathway; Cancer
• ISSN: 1738-7698; 2288-2529; 2283-2529
• DOI: 10.15188/kjopp.2020.08.34.4.177

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.