scholarly journals FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells

The Prostate ◽  
2015 ◽  
Vol 75 (9) ◽  
pp. 976-987 ◽  
Author(s):  
Wenhuan Guo ◽  
Anne L. Keener ◽  
Yifeng Jing ◽  
Liquan Cai ◽  
Junkui Ai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Transcriptional Activity ◽  
Prostate Cancer Cells ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals CMTM5-v1 inhibits cell proliferation and migration by downregulating oncogenic EGFR signaling in prostate cancer cells

2020 ◽  
Vol 11 (13) ◽  
pp. 3762-3770 ◽  
Author(s):  
Yeqing Yuan ◽  
Zhengzuo Sheng ◽  
Zhenhua Liu ◽  
Xiaowei Zhang ◽  
Yunbei Xiao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Egfr Signaling ◽  
Prostate Cancer Cells ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract 633: Protein Kinase D Regulates VEGFR-2 Transcriptional Activity in Endothelial Cells Through AP-2β

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Luke H Hoeppner ◽  
Resham Bhattacharya ◽  
Ying Wang ◽  
Ramcharan Singh Angom ◽  
Enfeng Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Binding Sites ◽  
Transcriptional Activity ◽  
Endothelial Cell Proliferation ◽  
Protein Kinase D ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Vascular endothelial growth factor A (VEGF) signals primarily through its cognate receptor VEGFR-2 to control vasculogenesis and angiogenesis. Dysregulation of these physiological processes contributes to the pathologies of heart disease, stroke, and cancer. Protein kinase D (PKD) plays a crucial role in the regulation of angiogenesis by modulating endothelial cell proliferation and migration. In human umbilical vein endothelial cells (HUVEC) and human blood outgrowth endothelial cells (BOEC), knockdown of PKD-1 or PKD-2 downregulates VEGFR-2 and significantly inhibits VEGF-induced endothelial cell proliferation and migration. We sought to determine the molecular mechanism through which PKD modulates VEGFR-2 expression. Based on bioinformatics data, activating enhancer binding protein 2 (AP2) binding sites exist within the VEGFR-2 promoter. Thus, we hypothesized PKD may downregulate VEGFR-2 through AP2-mediated transcriptional repression of the VEGFR-2 promoter. Indeed, AP2β binds the VEGFR-2 promoter upon PKD knockdown in HUVEC as evident by chromatin immunoprecipitation assay. Luciferase reporter assays using serial deletions of AP2β binding sites within the VEGFR-2 promoter revealed transcriptional activity negatively correlated with the number of AP2β binding sites, thus confirming negative regulation of VEGFR-2 transcription by AP2β. Next, using siRNA, we demonstrated that upregulation of AP2β decreased VEGFR-2 expression and loss of AP2β enhanced VEGFR-2 expression. In vivo studies confirmed this finding as we observed increased VEGFR-2 immunostaining in the dorsal horn of the spinal cord of embryonic day 13 AP2β knockout mice. We hypothesize that PKD directly regulates AP2β function by serine phosphorylation and ongoing studies are being conducted to determine phosphorylation sites in AP2β directly regulated by PKD. Taken together, we demonstrate AP2β negatively regulates VEGFR-2 transcription and VEGFR-2 is a major downstream target of PKD. Our findings describing how PKD regulates angiogenesis may contribute to the development of therapies to improve the clinical outcome of patients afflicted by heart disease, stroke, and cancer.

scholarly journals Silencing of ELK3 Induces S-M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yuanshen Mao ◽  
Wenfeng Li ◽  
Bao Hua ◽  
Xin Gu ◽  
Weixin Pan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Prostate Cancer Cells ◽  
Migration Inhibition ◽  
Akt Inhibitor ◽  
Phase Arrest ◽  
M Phase ◽  
And Migration

ELK3, an ETS domain-containing transcription factor, participates in various physiological and pathological processes including cell proliferation, migration, angiogenesis, and malignant progression. However, the role of ELK3 in prostate cancer cells and its mechanism are not fully understood. The contribution of ELK3 to prostate cancer progression was investigated in the present study. We showed that silencing of ELK3 by siRNA in prostate cancer cell DU145 induced S-M phase arrest, promoted apoptosis, inhibited cell proliferation and migration in vitro, and suppressed xenograft growth in mice in vivo. In accordance with its ability to arrest cells in S-M phase, the expression of cyclin A and cyclin B was downregulated. In addition, the expression of p53 was upregulated following ELK3 knockdown, while that of antiapoptotic Bcl-2 was decreased. The migration inhibition may partly due to upregulation of SERPINE1 (a serine protease inhibitor) followed ELK3 knockdown. Consistently, downregulation of SERPINE1 resulted in a modest elimination of migration inhibition resulted from ELK3 knockdown. Furthermore, we found that the AKT signaling was activated in ELK3 knockdown cells, and treatment these cells with AKT inhibitor attenuated SERPINE1 expression induced by ELK3 silencing, suggesting that activation of AKT pathway may be one of the reasons for upregulation of SERPINE1 after ELK3 knockdown. In conclusion, modulation of ELK3 expression may control the progression of prostate cancer partly by regulating cell growth, apoptosis, and migration.

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