상근피의 Hippo 신호전달 경로 활성화를 통한 YAP 억제 효능

• Published in: 동의생리병리학회지 Vol. 33; no. 4; pp. 191 - 197
• Main Authors: 조유나(You Na Cho), 최다빈(Da Bin Choi), 정한솔(Han Sol Jeong)
• Format: Journal Article
• Language: Korean
• Published: 한의병리학회 2019
• Subjects: 한의학; Root bark of Morus alba; Phos-taq; Hippo-YAP; Cancer
• ISSN: 1738-7698; 2288-2529; 2283-2529
• DOI: 10.15188/kjopp.2019.08.33.4.191

This study aims to evaluate the effects of the root bark of Morus alba (RMA) on the regulation of the Hippo-YAP pathway. Hippo-YAP signaling is a critical regulator in controlling organ size and tissue homeostasis. Hippo, the serine/threonine kinase phosphorylate the LATS. Phosphorylated LATS then phosphorylates and inactivates the YAP and TAZ, which are two closely related transcriptional co-activator. Here we report RMA activates the Hippo signaling, thereby inhibits the YAP/TAZ activity. First, we examine the cytotoxic effects of RMA by MTT assay. RMA was cytotoxic at concentrations higher than $50{\mu}g/ml$ in HEK293A cells. The reporter gene assay was performed to measure the activity of TEAD, a key transcription factor that controls cell growth and proliferation. RMA significantly suppressed the luciferase activity. By phos-taq gel shift assay, and western blotting, we showed that RMA enhanced the phosphorylation of YAP in wild type cells, but not in LATS1/2 knock out cells, which means RMA activates classical Hippo pathway. RMA induced the cytoplasmic sequestration of YAP. RMA also suppressed the mRNA expression of CTGF and CYR61; the two major YAP dependent genes. Taken together, RMA is considered to be a good candidate for proliferative disease such as cancer, by facilitating cell death through activating the Hippo signaling pathway.