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

doi:10.3390/cells11132031

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 journal › Article › peer-review

4 Citations (Scopus)

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 language	English
Article number	2031
Journal	Cells
Volume	11
Issue number	13
DOIs	https://doi.org/10.3390/cells11132031
Publication status	Published - 2022 Jul 1

Keywords

LMO2
STAT3
cancer stem cells
glioblastoma
glioma stem cells

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cells11132031

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

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.",

keywords = "LMO2, STAT3, cancer stem cells, glioblastoma, glioma stem cells",

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

note = "Funding Information: Funding: This work was supported by grants from the National Research Foundation (NRF) (2017R1E1A1A01074205 and 2020R1A2C2099668) and the School of Life Sciences and Biotechnology for BK21 Plus, Korea University. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/cells11132031",

language = "English",

volume = "11",

journal = "Cells",

issn = "2073-4409",

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TY - JOUR

T1 - Cytoplasmic LMO2-LDB1 Complex Activates STAT3 Signaling through Interaction with gp130-JAK in Glioma Stem Cells

AU - Park, Cheol Gyu

AU - Choi, Sang Hun

AU - Lee, Seon Yong

AU - Eun, Kiyoung

AU - Park, Min Gi

AU - Jang, Junseok

AU - Jeong, Hyeon Ju

AU - Kim, Seong Jin

AU - Jeong, Sohee

AU - Lee, Kanghun

AU - Kim, Hyunggee

N1 - Funding Information: Funding: This work was supported by grants from the National Research Foundation (NRF) (2017R1E1A1A01074205 and 2020R1A2C2099668) and the School of Life Sciences and Biotechnology for BK21 Plus, Korea University. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/7/1

Y1 - 2022/7/1

N2 - 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.

AB - 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.

KW - LMO2

KW - STAT3

KW - cancer stem cells

KW - glioblastoma

KW - glioma stem cells

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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