TRIB2 Stimulates Cancer Stem-Like Properties through Activating the AKT-GSK3ββ-ββ-Catenin Signaling Axis

• Published in: Molecules and cells pp. 481 - 492
• Main Authors: Dae Kyoung Kim, 김유나, Ye Eun Kim, Seo Yul Lee, Min Joo Shin, Eun Kyoung Do, 최경운, 김승철, 김기형, 서동수, 송박용, 김재호
• Format: Journal Article
• Language: English
• Published: 한국분자세포생물학회 01.07.2021
• Subjects: 생물학
• ISSN: 1016-8478; 0219-1032

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 phosphoinositide-3-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. KCI Citation Count: 2