ETS transcription factors Etv2 and Fli1b are required for tumor angiogenesis

Baltrunaite, Kristina; Craig, Michael P.; Desai, Sharina Palencia; Chaturvedi, Praneet; Pandey, Ram Naresh; Hegde, Rashmi S.; Sumanas, Saulius

doi:10.1007/s10456-017-9539-8

Cited by 30 publications

(20 citation statements)

References 33 publications

(54 reference statements)

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“…ETV5 has also been shown to trigger the transcription of MMP‐2, TIMP, and other proteinases to modify the extracellular matrix in human chondrosarcoma . Additionally, previous studies have indicated that other ETS members, such as ETS1, ETS2, ETV2 and ETV4 regulate tumor angiogenesis . Our study showed that ETV5 can regulate angiogenesis in the context of CRC.…”

Section: Discussionsupporting

confidence: 58%

“…28 Additionally, previous studies have indicated that other ETS members, such as ETS1, ETS2, ETV2 and ETV4 regulate tumor angiogenesis. [29][30][31] Our study showed that ETV5 can regulate angiogenesis in the context of CRC. Importantly, ETV5 and its direct target, PDGF-BB, tend to be co-overexpressed in CRC, and CRC with both genes upregulated exhibits the worst prognosis ( Fig.…”

Section: Discussionmentioning

confidence: 63%

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ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

Cheng

Jin

et al. 2019

Intl Journal of Cancer

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ETS transcription factors play important roles in tumor cell invasion, differentiation and angiogenesis. In this study, we initially demonstrated that ETS translocation variant 5 (ETV5) is abnormally upregulated in colorectal cancer (CRC), is positively correlated with CRC tumor size, lymphatic metastasis and tumor node metastasis (TNM) stage and indicates shorter survival and disease‐free survival in CRC patients. In vitro and in vivo experiments revealed that the downregulation of ETV5 could significantly suppress CRC cell proliferation. Moreover, overexpression of ETV5 could stimulate CRC angiogenesis in vitro and in vivo, which is consistent with RNA‐seq results. Then, we identified platelet‐derived growth factor BB (PDGF‐BB) as a direct target of ETV5 that plays an important role in ETV5‐mediated CRC angiogenesis through an angiogenesis antibody microarray. Additionally, PDGF‐BB could activate VEGFA expression via the PDGFR‐β/Src/STAT3 pathway in CRC cells and appeared to be positively correlated with ETV5 in CRC tissues. Finally, we revealed that ETV5 could bind directly to the promoter region of PDGF‐BB and regulate its expression through ChIP and luciferase assays. Overall, our study suggested that the transcription factor ETV5 could stimulate CRC malignancy and promote CRC angiogenesis by directly targeting PDGF‐BB. These findings suggest that EVT5 may be a potential new diagnostic and prognostic marker in CRC and that targeting ETV5 might be a potential therapeutic option for inhibiting CRC angiogenesis.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 63%

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

Cheng

Jin

et al. 2019

Intl Journal of Cancer

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“…The ETS transcription factors ETV2, FLI1, and ERG1 act early to specify pluripotent cells toward the EC lineage (24). ETV2 alone drives vasculogenesis, whereas ETV2 and FLI1 act redundantly during angiogenesis (25). ERG1 promotes vascular differentiation and stability through Wnt/ß-catenin signaling (26).…”

Section: Transcriptional Regulation Of Ec Specification and Differentmentioning

confidence: 99%

Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology

Augustin

Koh

2017

Science

550

456

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Blood vessels form one of the body's largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism, as well as in cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (ECs), whose cellular and molecular heterogeneity has long been recognized. Yet distinct organotypic functional attributes and the molecular mechanisms controlling EC differentiation and vascular bed-specific functions have only become known in recent years. Considering the involvement of vascular dysfunction in numerous chronic and life-threatening diseases, a better molecular understanding of organotypic vasculatures may pave the way toward novel angiotargeted treatments to cure hitherto intractable diseases. This Review summarizes recent progress in the understanding of organotypic vascular differentiation and function.

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“…E26 transformation-speci c variant 5 (ETV5), a member of the ETS family, has been reported to be involved in the progression of hematologic malignancies, endometrial cancer [11,12], ovarian cancer [13,14], prostate cancer and thyroid cancer [15,16]. Some previous studies also revealed that the ETS family triggered angiogenesis in multiple tumors [13,17,18]. Similarly, our previous study showed that ETV5 facilitated CRC angiogenesis via PDGF-BB/Src/STAT3/VEGFA signaling pathway [19].…”

Section: Introductionmentioning

confidence: 84%

Targeting tumor cell-derived CCL2 as a strategy to overcome bevacizumab resistance in ETV5+ colorectal cancer

Feng

Liu

Liang

et al. 2020

Preprint

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Background ETV5 mediated angiogenesis was dependent on PDGF-BB/PDGFR-β/Src/STAT3/VEGFA pathway in colorectal cancer (CRC) in our previous study. However, whether ETV5 affects effect of antiangiogenic therapy in CRC requires further investigation. Methods GSEA analysis and a series of experiments were performed to identify the critical candidate gene involved in bevacizumab resistance, and further explored whether the treatment targeting the candidate gene enhanced bevacizumab sensitivity in vitro and in vivo. Results ETV5 could directly bind to VEGFA promoter and promote translation of VEGFA. However, by in vitro and in vivo experiments, ETV5 actually accelerated anti-VEGF therapy (bevacizumab) resistance. GSEA analysis and further assays confirmed that ETV5 could promote angiogenesis by enhancing secretion of another tumor angiogenesis factor CCL2 in CRC cells, which resulted in bevacizumab resistance. ETV5 induced VEGFA and CCL2 were mutually independent to induce angiogenesis by activating PI3K/AKT and p38/MAPK signaling pathways in human umbilical vein endothelial cells. In CRC tissues, ETV5 protein level was positively associated with CD31, CCL2, VEGFA protein expression. CRC patients with high expression of ETV5/VEGFA or ETV5/CCL2 showed inferior prognosis than other patients. Combination of anti-CCL2 and anti-VEGFA (Bevacizumab) treatment could more effectively inhibited tumor angiogenesis and growth than single treatment did in CRCs with high expression of ETV5 (ETV5 + CRCs). Conclusions Our results not only revealed ETV5 as a novel biomarker for antiangiogenic therapy, but also indicated a potential combined therapy strategy by simultaneously targeting CCL2 and VEGFA in ETV5 + CRC.

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ETS transcription factors Etv2 and Fli1b are required for tumor angiogenesis

Cited by 30 publications

References 33 publications

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology

Targeting tumor cell-derived CCL2 as a strategy to overcome bevacizumab resistance in ETV5+ colorectal cancer

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