EVI1 overexpression promotes ovarian cancer progression by regulating estrogen signaling. (20th August 2021)

• Record Type: Journal Article
• Authors: Wang, Zixiang; Li, Yingwei; Wang, Nan; Li, Peng; Kong, Beihua; Liu, Zhaojian
• Is Part Of: Molecular and cellular endocrinology. Volume 534(2021)
• Publication Date: 2021-08-20
• Subjects: EVI1 -- ESR1 -- Estrogen signaling -- Ovarian cancer; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2021.111367
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: High-grade serous ovarian cancer (HGSOC) is characterized by TP53 mutation and somatic copy number alterations (SCNAs). Here we show that the oncogenic transcription factor EVI1 (ecotropic viral integration site-1) is amplified and overexpressed up to 30% of 1640 HGSOC cases in The Cancer Genome Atlas (TCGA). Functionally, EVI1 promotes proliferation/invasion in vitro and tumor growth of xenograft model in vivo . Importantly, we discover that EVI1 regulates estrogen signaling by directly activating ESR1 (estrogen receptor 1) transcription determined by the ChIP and luciferase assay. Interestingly, EVI1 and ESR1 share common regulatory targets as indicated by the analysis of ChIP-Seq data. EVI1 and ESR1 collaborate in the regulation of some estrogen receptor-regulated genes. Furthermore, EVI1 drives tumor aggressiveness partially by regulating estrogen signaling. Estrogen enhances the proliferation, invasion and xenograft growth of ovarian cancer cells. Importantly, estrogen can rescue the inhibition of proliferation, invasion and xenograft growth induced by silencing EVI1. These findings suggest that EVI1 functions as a novel regulator of the estrogen signaling network in ovarian cancer. Highlights: EVI1 is ubiquitously amplified and overexpressed in high-grade serous ovarian cancer. EVI1 induces ESR1 transcription by directly binding to its promoter in ovarian cancer. EVI1 coregulates the ESR1 transcription program and reinforces estrogen signaling. EVI1-induced ESR1 signaling activation is required for ovarian cancer progression.