Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R

Seung Hee Seo; Soo Yeon Hwang; Seohui Hwang; Sunjung Han; Hyojin Park; Yun Sil Lee; Seung Bae Rho; Youngjoo Kwon

doi:10.15252/embr.202152977

Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R

Seung Hee Seo, Soo Yeon Hwang, Seohui Hwang, Sunjung Han, Hyojin Park, Yun Sil Lee, Seung Bae Rho, Youngjoo Kwon

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers despite a relatively low incidence. Angiogenesis, one of the hallmarks of cancer, is essential for the pathogenesis of EOC, which is related to the induction of angiogenic factors. We found that ELF3 was highly expressed in EOCs under hypoxia and functioned as a transcription factor for IGF1. The ELF3-mediated increase in the secretion of IGF1 and VEGF promoted endothelial cell proliferation, migration, and EOC angiogenesis. Although this situation was much exaggerated under hypoxia, ELF3 silencing under hypoxia significantly attenuated angiogenic activity in endothelial cells by reducing the expression and secretion of IGF1 and VEGF. ELF3 silencing attenuated angiogenesis and tumorigenesis in ex vivo and xenograft mouse models. Consequently, ELF3 plays an important role in the induction of angiogenesis and tumorigenesis in EOC as a transcription factor of IGF1. A detailed understanding of the biological mechanism of ELF3 may both improve current antiangiogenic therapies and have anticancer effects for EOC.

Original language	English
Article number	e52977
Journal	EMBO Reports
Volume	23
Issue number	8
DOIs	https://doi.org/10.15252/embr.202152977
State	Published - 3 Aug 2022

Bibliographical note

Funding Information:
This work was supported by the Health Fellowship Foundation and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2018R1A5A2025286) and by the Bio & Medical Technology Development Program of the NRF funded by MSIT (2021M3E5E7024855).

Publisher Copyright:
© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Keywords

ELF3
hypoxia
insulin-like growth factor I
ovarian cancer
tumor angiogenesis

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title = "Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R",

abstract = "Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers despite a relatively low incidence. Angiogenesis, one of the hallmarks of cancer, is essential for the pathogenesis of EOC, which is related to the induction of angiogenic factors. We found that ELF3 was highly expressed in EOCs under hypoxia and functioned as a transcription factor for IGF1. The ELF3-mediated increase in the secretion of IGF1 and VEGF promoted endothelial cell proliferation, migration, and EOC angiogenesis. Although this situation was much exaggerated under hypoxia, ELF3 silencing under hypoxia significantly attenuated angiogenic activity in endothelial cells by reducing the expression and secretion of IGF1 and VEGF. ELF3 silencing attenuated angiogenesis and tumorigenesis in ex vivo and xenograft mouse models. Consequently, ELF3 plays an important role in the induction of angiogenesis and tumorigenesis in EOC as a transcription factor of IGF1. A detailed understanding of the biological mechanism of ELF3 may both improve current antiangiogenic therapies and have anticancer effects for EOC.",

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author = "Seo, {Seung Hee} and Hwang, {Soo Yeon} and Seohui Hwang and Sunjung Han and Hyojin Park and Lee, {Yun Sil} and Rho, {Seung Bae} and Youngjoo Kwon",

note = "Funding Information: This work was supported by the Health Fellowship Foundation and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2018R1A5A2025286) and by the Bio & Medical Technology Development Program of the NRF funded by MSIT (2021M3E5E7024855). Publisher Copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",

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AU - Seo, Seung Hee

AU - Hwang, Soo Yeon

AU - Hwang, Seohui

AU - Han, Sunjung

AU - Park, Hyojin

AU - Lee, Yun Sil

AU - Rho, Seung Bae

AU - Kwon, Youngjoo

N1 - Funding Information: This work was supported by the Health Fellowship Foundation and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2018R1A5A2025286) and by the Bio & Medical Technology Development Program of the NRF funded by MSIT (2021M3E5E7024855). Publisher Copyright: © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

PY - 2022/8/3

Y1 - 2022/8/3

N2 - Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers despite a relatively low incidence. Angiogenesis, one of the hallmarks of cancer, is essential for the pathogenesis of EOC, which is related to the induction of angiogenic factors. We found that ELF3 was highly expressed in EOCs under hypoxia and functioned as a transcription factor for IGF1. The ELF3-mediated increase in the secretion of IGF1 and VEGF promoted endothelial cell proliferation, migration, and EOC angiogenesis. Although this situation was much exaggerated under hypoxia, ELF3 silencing under hypoxia significantly attenuated angiogenic activity in endothelial cells by reducing the expression and secretion of IGF1 and VEGF. ELF3 silencing attenuated angiogenesis and tumorigenesis in ex vivo and xenograft mouse models. Consequently, ELF3 plays an important role in the induction of angiogenesis and tumorigenesis in EOC as a transcription factor of IGF1. A detailed understanding of the biological mechanism of ELF3 may both improve current antiangiogenic therapies and have anticancer effects for EOC.

AB - Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers despite a relatively low incidence. Angiogenesis, one of the hallmarks of cancer, is essential for the pathogenesis of EOC, which is related to the induction of angiogenic factors. We found that ELF3 was highly expressed in EOCs under hypoxia and functioned as a transcription factor for IGF1. The ELF3-mediated increase in the secretion of IGF1 and VEGF promoted endothelial cell proliferation, migration, and EOC angiogenesis. Although this situation was much exaggerated under hypoxia, ELF3 silencing under hypoxia significantly attenuated angiogenic activity in endothelial cells by reducing the expression and secretion of IGF1 and VEGF. ELF3 silencing attenuated angiogenesis and tumorigenesis in ex vivo and xenograft mouse models. Consequently, ELF3 plays an important role in the induction of angiogenesis and tumorigenesis in EOC as a transcription factor of IGF1. A detailed understanding of the biological mechanism of ELF3 may both improve current antiangiogenic therapies and have anticancer effects for EOC.

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Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R

Abstract

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Keywords

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