WT1 regulates murine hematopoiesis via maintenance of VEGF isoform ratio

Cunningham, Thomas J.; Palumbo, Ilaria; Grosso, Michela; Slater, Nicholas J.; Miles, Colin

doi:10.1182/blood-2012-11-466086

Cited by 15 publications

(21 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, our work shows a differential effect of individual WT1 isoforms on the internal, better characterized VEGF splice sites. Similar results were reported by Cunningham et al who showed that loss of WT1 expression in hematopoietic progenitor cells results in an abnormal profile of VEGF isoforms [42]. We did not evaluate which exon 8 was included, but since both WT1A and WT1D increase angiogenesis, it is unlikely that either isoform alone increases the use of exon 8b (which is antiangiogenic) over exon 8a.…”

Section: Discussionsupporting

confidence: 65%

WT1 regulates angiogenesis in Ewing Sarcoma

et al. 2014

View full text Add to dashboard Cite

Angiogenesis is required for tumor growth. WT1, a protein that affects both mRNA transcription and splicing, has recently been shown to regulate expression of vascular endothelial growth factor (VEGF), one of the major mediators of angiogenesis. In the present study, we tested the hypothesis that WT1 is a key regulator of tumor angiogenesis in Ewing sarcoma. We expressed exogenous WT1 in the WT1-null Ewing sarcoma cell line, SK-ES-1, and we suppressed WT1 expression using shRNA in the WT1-positive Ewing sarcoma cell line, MHH-ES. Suppression of WT1 in MHH-ES cells impairs angiogenesis, while expression of WT1 in SK-ES-1 cells causes increased angiogenesis. Different WT1 isoforms result in vessels with distinct morphologies, and this correlates with preferential upregulation of particular VEGF isoforms. WT1-expressing tumors show increased expression of pro-angiogenic molecules such as VEGF, MMP9, Ang-1, and Tie-2, supporting the hypothesis that WT1 is a global regulator of angiogenesis. We also demonstrate that WT1 regulates the expression of a panel of pro-angiogenic molecules in Ewing sarcoma cell lines. Finally, we found that WT1 expression is correlated with VEGF expression, MMP9 expression, and microvessel density in samples of primary Ewing sarcoma. Thus, our results demonstrate that WT1 expression directly regulates tumor angiogenesis by controlling the expression of a panel of pro-angiogenic genes.

show abstract

Section: Discussionsupporting

confidence: 65%

WT1 regulates angiogenesis in Ewing Sarcoma

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In studying the relationship between WT1 and vEGF, an important growth factor in cancer, loss of WT1 results in increased abundance of isoform vEGF-a120, while transfection of WT1 results in exon inclusion and loss of the 120 isoform. This demonstrates that WT1 is essential for controlling the splicing of vEGF-a (48). studies of the vEGF-b isoform have also shown alteration of splicing patterns with WT1 manipulation.…”

Section: Role Of Transcription Factor Binding On Splicingmentioning

confidence: 74%

Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review)

Avin

Umbricht

Zeiger

2016

International Journal of Oncology

View full text Add to dashboard Cite

The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), plays an essential role in telomere maintenance to oppose cellular senescence and, is highly regulated in normal and cancerous cells. Regulation of hTERT occurs through multiple avenues, including a unique pattern of CpG promoter methylation and alternative splicing. Promoter methylation affects the binding of transcription factors, resulting in changes in expression of the gene. In addition to expression level changes, changes in promoter binding can affect alternative splicing in a cotranscriptional manner. The alternative splicing of hTERT results in either the full length transcript which can form the active telomerase complex with hTR, or numerous inactive isoforms. Both regulation strategies are exploited in cancer to activate telomerase, however, the exact mechanism is unknown. Therefore, unraveling the link between promoter methylation status and alternative splicing for hTERT could expose yet another level of hTERT regulation. In an attempt to provide insight into the cellular control of active telomerase in cancer, this review will discuss our current perspective on CpG methylation of the hTERT promoter region, summarize the different forms of alternatively spliced variants, and examine examples of transcription factor binding that affects splicing.

show abstract

“…This aspect of WT1 controlled paracrine or intercellular signaling, is furthermore highlighted by reports on the regulation of VEGF-A via WT1 [132,133]. More recent studies identified the essential role of WT1 in RNA splicing of VEGF isoforms [134,135]. For example, it was demonstrated that WT1 mutant cells failed to repress the splicing-factor kinase SRPK1 resulting in altered splicing of VEGF isoforms, turning cells overall in a proangiogenic state [134].…”

Section: Regulatory Network Of Glomerular Development -Is Transcriptmentioning

confidence: 93%

Glomerular development – Shaping the multi-cellular filtration unit

Schell

Wanner

Huber

2014

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

The glomerulus represents a highly structured filtration unit, composed of glomerular endothelial cells, mesangial cells, podocytes and parietal epithelial cells. During glomerulogenesis an intricate network of signaling pathways involving transcription factors, secreted factors and cell-cell communication is required to guarantee accurate evolvement of a functional, complex 3-dimensional glomerular architecture. Here, we want to provide an overview on the critical steps and relevant signaling cascades of glomerular development.

show abstract

WT1 regulates murine hematopoiesis via maintenance of VEGF isoform ratio

Cited by 15 publications

References 18 publications

WT1 regulates angiogenesis in Ewing Sarcoma

WT1 regulates angiogenesis in Ewing Sarcoma

Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review)

Glomerular development – Shaping the multi-cellular filtration unit

Contact Info

Product

Resources

About