Cytoplasmic LMO2-LDB1 Complex Activates STAT3 Signaling through Interaction with gp130-JAK in Glioma Stem Cells

Cheol Gyu Park, Sang Hun Choi, Seon Yong Lee, Kiyoung Eun, Min Gi Park, Junseok Jang, Hyeon Ju Jeong, Seong Jin Kim, Sohee Jeong, Kanghun Lee, Hyunggee Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The oncogenic role of nuclear LIM domain only 2 (LMO2) as a transcriptional regulator is well established, but its function in the cytoplasm is largely unknown. Here, we identified LMO2 as a cytoplasmic activator for signal transducer and activator of transcription 3 (STAT3) signaling in glioma stem cells (GSCs) through biochemical and bioinformatics analyses. LMO2 increases STAT3 phosphorylation by interacting with glycoprotein 130 (gp130) and Janus kinases (JAKs). LMO2-driven activation of STAT3 signaling requires the LDB1 protein and leads to increased expression of an inhibitor of differentiation 1 (ID1), a master regulator of cancer stemness. Our findings indicate that the cytoplasmic LMO2-LDB1 complex plays a crucial role in the activation of the GSC signaling cascade via interaction with gp130 and JAK1/2. Thus, LMO2-LDB1 is a bona fide oncogenic protein complex that activates either the JAK-STAT signaling cascade in the cytoplasm or direct transcriptional regulation in the nucleus.

Original languageEnglish
Article number2031
JournalCells
Volume11
Issue number13
DOIs
Publication statusPublished - 2022 Jul 1

Keywords

  • LMO2
  • STAT3
  • cancer stem cells
  • glioblastoma
  • glioma stem cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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