探究肿瘤干细胞成因
The role of vascular endothelial growth factor (VEGF) signaling in cancer is not only well known in the context of angiogenesis but also important in the functional regulation of tumor cells.
癌症中的血管内皮细胞增长因子(VEGF)信号通路不仅在血管增生中很有名，在癌细胞的功能调控中也非常重要。
Autocrine VEGF signaling mediated by its co-receptors called neuropilins (NRPs) appears to be essential for sustaining the proliferation and survival of cancer stem cells (CSCs), which are implicated in mediating tumor growth, progression, and drug resistance.
由叫做神经素（NRP）的辅助受体调节的自分泌VEGF信号通路似乎对维持肿瘤干细胞（CSC）的增殖和存活是非常基础的，而这又与调控肿瘤生长，发展和耐药性有关。
Therefore, understanding the mechanisms involved in VEGF-mediated support of CSCs is critical to successfully treating cancer patients.
因此，理解由VEGF介导的对CSC的支持行为的相关机理对于成功治疗癌症患者是非常重要的。
The expression of the Hippo effector TAZ is associated with breast CSCs and confers stem cell–like properties.
河马效应器TAZ的表达与乳腺癌干细胞和干细胞样特性的获得相关。
We found that VEGF-NRP2 signaling contributed to the activation of TAZ in various breast cancer cells, which mediated a positive feedback loop that promoted mammosphere formation.
我们发现VEGF-NRP2信号促进了不同乳腺癌细胞中TAZ的激活，从而促进了一个正向的反馈回路，促进了非黏附性乳腺球群细胞的形成。
VEGF-NRP2 signaling activated the GTPase Rac1, which inhibited the Hippo kinase LATS, thus leading to TAZ activity.
VEGF-NRP2信号通路会激活GTP酶Rac1，而该酶会抑制河马信号激酶LATS，从而导致TAZ的活化。
In a complex with the transcription factor TEAD, TAZ then bound and repressed the promoter of the gene encoding the Rac GTPase-activating protein (Rac GAP) β2-chimaerin.
TAZ后来与转录因子联合成复合物TEAD，会抑制编码Rac GTP酶活化蛋白（Rac GAP）即 β2嵌合体的基因启动子。
By activating GTP hydrolysis, Rac GAPs effectively turn off Rac signaling; hence, the TAZ-mediated repression of β2-chimaerin resulted in sustained Rac1 activity in CSCs.
通过激活GTP的水解作用， Rac Gap可以有效关闭Rac信号通路；因此， TAZ-介导的对β2嵌合体的抑制会导致Rac1在肿瘤干细胞中的持续性活力。
Depletion of β2-chimaerin in non-CSCs increased Rac1 activity, TAZ abundance, and mammosphere formation.
在非肿瘤干细胞中去掉β2嵌合体会增加Rac1的活性， TAZ的积累以及非黏附性乳腺球群细胞的形成。
Analysis of a breast cancer patient database revealed an inverse correlation between β2-chimaerin and TAZ expression in tumors.
对乳腺癌患者数据库的分析显示β2嵌合体和肿瘤中的TAZ表达呈负相关。
These findings highlight an unexpected role for β2-chimaerin in a feed-forward loop of TAZ activation and the acquisition of CSC properties.
这些研究突出了β2嵌合体在TAZ活化的前馈回路和CSC性质获得中的意外作用。
VEGF–neuropilin-2 signaling promotes stem-like traits in breast cancer cells by TAZ-mediated repression of the Rac GAP β2-chimaerin
Ameer L. Elaimy, Santosh Guru， et al.
Sci. Signal. 01 May 2018:
Vol. 11, Issue 528, eaao6897
DOI: 10.1126/scisignal.aao6897
感谢关注
跟amber 一起看世界