Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition
文献类型：期刊论文
| 作者 | Zhao, Wencao3; Cao, Le3; Zhang, Wenjuan3; Li, Dantong3; Xue, Wenzhi3; Wu, Shuang3; Cao, Mengye3; Fu, Cong3; Qi, Haonan3; Hao, Yimei3 |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2019 |
| 卷号 | 29期号:11页码:895-910 |
| 关键词 | FAM122A SUMO1 modification PP2A Ubiquitination Phosphatase activity |
| ISSN号 | 1001-0602 |
| DOI | 10.1038/s41422-019-0229-5 |
| 文献子类 | Article |
| 英文摘要 | The response of endothelial cells to signaling stimulation is critical for vascular morphogenesis, homeostasis and function. Vascular endothelial growth factor-a (VEGFA) has been commonly recognized as a pro-angiogenic factor in vertebrate developmental, physiological and pathological conditions for decades. Here we report a novel finding that genetic ablation of CDP-diacylglycerol synthetase-2 (CDS2), a metabolic enzyme that controls phosphoinositide recycling, switches the output of VEGFA signaling from promoting angiogenesis to unexpectedly inducing vessel regression. Live imaging analysis uncovered the presence of reverse migration of the angiogenic endothelium in cds2 mutant zebrafish upon VEGFA stimulation, and endothelium regression also occurred in postnatal retina and implanted tumor models in mice. In tumor models, CDS2 deficiency enhanced the level of tumor-secreted VEGFA, which in-turn trapped tumors into a VEGFA-induced vessel regression situation, leading to suppression of tumor growth. Mechanistically, VEGFA stimulation reduced phosphatidylinositol (4,5)-bisphosphate (PIP2) availability in the absence of CDS2-controlled-phosphoinositide metabolism, subsequently causing phosphatidylinositol (3,4,5)-triphosphate (PIP3) deficiency and FOXO1 activation to trigger regression of CDS2-null endothelium. Thus, our data indicate that the effect of VEGFA on vasculature is context-dependent and can be converted from angiogenesis to vascular regression. |
| 学科主题 | Biochemistry & Molecular Biology ; Biophysics |
| WOS关键词 | GROWTH-FACTOR VEGF ; PHOSPHATIDIC-ACID ; VESSEL REGRESSION ; CELL BEHAVIOR ; IN-VIVO ; ANGIOGENESIS ; EXPRESSION ; ZEBRAFISH ; NOTCH ; MECHANISMS |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31501519 |
| WOS记录号 | WOS:000494989000006 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/673]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai, Peoples R China; 2.Yale Univ, Sch Med, Dept Pharmacol, Vasc Biol & Therapeut Program, New Haven, CT 06510 USA, 3.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Key Lab Tissue Microenvironm & Tumor,CAS Ctr Exce, Shanghai, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China; 5.East China Normal Univ, Sch Life Sci, Inst Mol Med, Shanghai Key Lab Regulatory Biol, Shanghai, Peoples R China; 6.Innovat Res Team High Level Local Univ Shanghai, Shanghai, Peoples R China; 7.Zhejiang Univ, Coll Life Sci, Inst Genet, Hangzhou, Zhejiang, Peoples R China; 8.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhao, Wencao,Cao, Le,Zhang, Wenjuan,et al. Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition[J]. CELL RESEARCH,2019,29(11):895-910. |
| APA | Zhao, Wencao.,Cao, Le.,Zhang, Wenjuan.,Li, Dantong.,Xue, Wenzhi.,...&,.(2019).Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition.CELL RESEARCH,29(11),895-910. |
| MLA | Zhao, Wencao,et al."Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition".CELL RESEARCH 29.11(2019):895-910. |
入库方式： OAI收割
来源：上海营养与健康研究所
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