Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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TRIB2 Stimulates Cancer Stem-Like Properties through Activating the AKT-GSK3β-β-Catenin Signaling Axis

  • Kim, Dae Kyoung (Department of Physiology, School of Medicine, Pusan National University) ;
  • Kim, Yu Na (Department of Physiology, School of Medicine, Pusan National University) ;
  • Kim, Ye Eun (Department of Physiology, School of Medicine, Pusan National University) ;
  • Lee, Seo Yul (Department of Physiology, School of Medicine, Pusan National University) ;
  • Shin, Min Joo (Department of Physiology, School of Medicine, Pusan National University) ;
  • Do, Eun Kyoung (Department of Physiology, School of Medicine, Pusan National University) ;
  • Choi, Kyung-Un (Department of Pathology, School of Medicine, Pusan National University) ;
  • Kim, Seung-Chul (Department of Obstetrics and Gynecology, School of Medicine, Pusan National University) ;
  • Kim, Ki-Hyung (Department of Obstetrics and Gynecology, School of Medicine, Pusan National University) ;
  • Suh, Dong-Soo (Department of Obstetrics and Gynecology, School of Medicine, Pusan National University) ;
  • Song, Parkyong (Department of Convergence Medicine, School of Medicine, Pusan National University) ;
  • Kim, Jae Ho (Department of Physiology, School of Medicine, Pusan National University)
  • Received : 2021.02.03
  • Accepted : 2021.05.12
  • Published : 2021.07.31
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Abstract

Tribbles homolog 2 (TRIB2) is implicated in tumorigenesis and drug resistance in various types of cancers. However, the role of TRIB2 in the regulation of tumorigenesis and drug resistance of cancer stem cells (CSCs) is still elusive. In the present study, we showed increased expression of TRIB2 in spheroid-forming and aldehyde dehydrogenase-positive CSC populations of A2780 epithelial ovarian cancer cells. Short hairpin RNA-mediated silencing of TRIB2 expression attenuates the spheroid-forming, migratory, tumorigenic, and drug-resistant properties of A2780 cells, whereas overexpression of TRIB2 increases the CSC-like characteristics. TRIB2 overexpression induced GSK3β inactivation by augmenting AKT-dependent phosphorylation of GSK3β at Ser9, followed by increasing β-catenin level via reducing the GSK3β-mediated phosphorylation of β-catenin. Treatment of TRIB2-ovexpressed A2780 cells with the phosphoinositide3-kinase inhibitor LY294002 abrogated TRIB2-stimulated proliferation, migration, drug resistance of A2780 cells. These results suggest a critical role for TRIB2 in the regulation of CSC-like properties by increasing the stability of β-catenin protein via the AKT-GSK3β-dependent pathways.

Keywords

Acknowledgement

Support for this research was by the MRC programs (NRF-2015R1A5A2009656) of the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2020R1I1A3073064; NRF-2020R1A2C2011880) and the 2019 Post-Doc Development program of Pusan National University.

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