Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R

被引：22

作者：

Seo, Seung Hee ^{[1
]}

Hwang, Soo-Yeon ^{[1
]}

Hwang, Seohui ^{[1
]}

Han, Sunjung ^{[1
]}

Park, Hyojin ^{[1
]}

Lee, Yun-Sil ^{[1
]}

Rho, Seung Bae ^{[2
]}

Kwon, Youngjoo ^{[1
]}

机构：

[1] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul, South Korea

[2] Natl Canc Ctr, Res Inst, Goyang Si Gyeonggi Do, South Korea

来源：

EMBO REPORTS | 2022年 / 23卷 / 08期

基金：

新加坡国家研究基金会;

关键词：

ELF3; hypoxia; insulin-like growth factor I; ovarian cancer; tumor angiogenesis; ENDOTHELIAL GROWTH-FACTOR; OVARIAN-CANCER; SIGNALING PATHWAYS; MAP KINASE; TRANSCRIPTION; METASTASIS; CELLS; REQUIREMENT; EXPRESSION; PI3K/AKT;

D O I：

10.15252/embr.202152977

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：17

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