A novel interplay between Rap1 and PKA regulates induction of angiogenesis in prostate cancer.
A novel interplay between Rap1 and PKA regulates induction of angiogenesis in prostate cancer.
复制标题
RAP1和PKA之间的一种新型相互作用调节前列腺癌中血管生成的诱导。
DOI：
10.1371/journal.pone.0049893
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Rosner MR
中科院分区：
文献类型：
--
作者：
Menon J;Doebele RC;Gomes S;Bevilacqua E;Reindl KM;Rosner MR
Angiogenesis inhibition is an important therapeutic strategy for advanced stage prostate cancer. Previous work from our laboratory showed that sustained stimulation of Rap1 by 8-pCPT-2'-O-Me-cAMP (8CPT) via activation of Epac, a Rap1 GEF, or by expression of a constitutively active Rap1 mutant (cRap1) suppresses endothelial cell chemotaxis and subsequent angiogenesis. When we tested this model in the context of a prostate tumor xenograft, we found that 8CPT had no significant effect on prostate tumor growth alone. However, in cells harboring cRap1, 8CPT dramatically inhibited not only prostate tumor growth but also VEGF expression and angiogenesis within the tumor microenvironment. Subsequent analysis of the mechanism revealed that, in prostate tumor epithelial cells, 8CPT acted via stimulation of PKA rather than Epac/Rap1. PKA antagonizes Rap1 and hypoxic induction of 1α protein expression, VEGF production and, ultimately, angiogenesis. Together these findings provide evidence for a novel interplay between Rap1, Epac, and PKA that regulates tumor-stromal induction of angiogenesis.
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影响因子：
20.3
作者：
Carmona, Guillaume;Goettig, Stephan;Chavakis, Emmanouil
通讯作者：
Chavakis, Emmanouil
影响因子：
5.3
作者：
Duchniewicz, M;Zemojtel, T;Zwartkiruis, FJT
通讯作者：
Zwartkiruis, FJT
影响因子：
2.8
作者：
Bigler, Dora;Gioeli, Daniel;Theodorescu, Dan
通讯作者：
Theodorescu, Dan
影响因子：
11.2
作者：
Bailey CL;Kelly P;Casey PJ
通讯作者：
Casey PJ
DOI：
10.1084/jem.20100040
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Awasthi A;Samarakoon A;Chu H;Kamalakannan R;Quilliam LA;Chrzanowska-Wodnicka M;White GC 2nd;Malarkannan S
通讯作者：
Malarkannan S