2. Academic Validation
  3. Regulation of Hippo-YAP signaling axis by Isoalantolactone suppresses tumor progression in cholangiocarcinoma

Regulation of Hippo-YAP signaling axis by Isoalantolactone suppresses tumor progression in cholangiocarcinoma

  • Transl Oncol. 2024 May 25:46:101971. doi: 10.1016/j.tranon.2024.101971.
Cho-Long Kim 1,  Su-Bin Lim 1,  Dong Hyun Kim 1,  Ye Eun Sim 1,  Li-Jung Kang 2,  Su Jung Park 3,  Hyungwoo Kim 4,  Tae Hoon Roh 5,  Jung-Soon Mo 6,  Han-Sol Jeong 7
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, Graduate School, Ajou University School of Medicine, Suwon 16499, South Korea.
  • 2 Three-Dimensional Immune System Imaging Core Facility, Ajou University, Suwon 16499, South Korea.
  • 3 Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, South Korea.
  • 4 Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, South Korea.
  • 5 Department of Neurosurgery, Ajou University School of Medicine, Suwon 16499, South Korea.
  • 6 Department of Biomedical Sciences, Graduate School, Ajou University School of Medicine, Suwon 16499, South Korea; Institute of Medical Science, Ajou University School of Medicine, Suwon 16499, South Korea. Electronic address: j5mo@ajou.ac.kr.
  • 7 Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, South Korea. Electronic address: jhsol33@pusan.ac.kr.
PMID: 38797019 DOI: 10.1016/j.tranon.2024.101971
Abstract

Cholangiocarcinoma (CCA) is a devastating malignancy characterized by aggressive tumor growth and limited treatment options. Dysregulation of the Hippo signaling pathway and its downstream effector, Yes-associated protein (YAP), has been implicated in CCA development and progression. In this study, we investigated the effects of Isoalantolactone (IALT) on CCA cells to elucidate its effect on YAP activity and its potential clinical significance. Our findings demonstrate that IALT exerts cytotoxic effects, induces Apoptosis, and modulates YAP signaling in SNU478 cells. We further confirmed the involvement of the canonical Hippo pathway by generating LATS1/LATS2 knockout cells, highlighting the dependence of IALT-mediated Apoptosis and YAP phosphorylation on the Hippo-LATS signaling axis. In addition, IALT suppressed cell growth and migration, partially dependent on YAP-TEAD activity. These results provide insights into the therapeutic potential of targeting YAP in CCA and provide a rationale for developing of YAP-targeted therapies for this challenging malignancy.

Keywords

Apoptosis; Cell growth; Cell migration; Cholangiocarcinoma; Hippo-YAP pathway; Isoalantolactone.

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