blockingautocrinevegfsignalingbysunitinibananticancerdrugpromotesembryonicstemcellselfrenewalandsomaticcellreprogramming
文献类型：期刊论文
| 作者 | Chen Guofang2; Xu Xinxiu2; Zhang Lihong2; Fu Yanbin1; Wang Min2; Gu Haifeng2 ; Xie Xin2
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| 刊名 | cellresearch
 |
| 出版日期 | 2014 |
| 卷号 | 24期号:9页码:1121 |
| ISSN号 | 1001-0602 |
| 关键词 | ENDOPLASMIC-RETICULUM STRESS GROWTH-FACTOR RECEPTORS TUMOR-CELLS FACTOR-I DIFFERENTIATION EXPRESSION HYPOXIA ANGIOGENESIS HIF-1-ALPHA INHIBITOR sunitinib Sutent embryonic stem cell self-renewal iPSC VEGF autocrine |
| DOI | 10.1038/cr.2014.112 |
| 英文摘要 | Maintaining the self-renewal of embryonic stem cells (ESCs) could be achieved by activating the extrinsic signaling, i.e., the use of leukemia inhibitory factor (LIF), or blocking the intrinsic differentiation pathways, i.e., the use of GSK3 and MEK inhibitors (2i). Here we found that even in medium supplemented with LIF, mESCs still tend to differentiate toward meso-endoderm lineages after long-term culture and the culture spontaneously secretes vascular endothelial growth factors (VEGFs). Blocking VEGF signaling with sunitinib, an anti-cancer drug and a receptor tyrosine kinase (RTK) inhibitor mainly targeting VEGF receptors (VEGFRs), is capable of maintaining the mESCs in the undifferentiated state without the need for feeder cells or LIF. Sunitinib facilitates the derivation of mESCs from blastocysts, and the mESCs maintained in sunitinib-containing medium remain pluripotent and are able to contribute to chimeric mice. Sunitinib also promotes iPSC generation from MEFs with only Oct4. Knocking down VEGFR2 or blocking it with neutralizing antibody mimicks the effect of sunitinib, indicating that blocking VEGF/VEGFR signaling is indeed beneficial to the self-renewal of mESCs. We also found that hypoxia-inducible factor alpha (HIF1 alpha) and endoplasmic reticulum (ER) stress are involved in the production of VEGF in mESCs. Blocking both pathways inhibits the expression of VEGF and prevents spontaneous differentiation of mESCs. Interestingly, LIF may also exert its effect by downregulating HIF1 alpha and ER stress pathways and subsequent VEGF expression. These results indicate the existence of an intrinsic differentiation pathway in mESCs by activating the autocrine VEGF signaling. Blocking VEGF signaling with sunitinib or other small molecules help to maintain the mESCs in the ground state of pluripotency. |
| 资助项目 | [Chinese Academy of Sciences] ; [Ministry of Science and Technology of China] ; [Shanghai Commission of Science and Technology] |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/286558]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.同济大学 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Chen Guofang,Xu Xinxiu,Zhang Lihong,et al. blockingautocrinevegfsignalingbysunitinibananticancerdrugpromotesembryonicstemcellselfrenewalandsomaticcellreprogramming[J]. cellresearch,2014,24(9):1121. |
| APA | Chen Guofang.,Xu Xinxiu.,Zhang Lihong.,Fu Yanbin.,Wang Min.,...&Xie Xin.(2014).blockingautocrinevegfsignalingbysunitinibananticancerdrugpromotesembryonicstemcellselfrenewalandsomaticcellreprogramming.cellresearch,24(9),1121. |
| MLA | Chen Guofang,et al."blockingautocrinevegfsignalingbysunitinibananticancerdrugpromotesembryonicstemcellselfrenewalandsomaticcellreprogramming".cellresearch 24.9(2014):1121. |
入库方式： OAI收割
来源：上海药物研究所
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