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Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53.


ABSTRACT: Focal adhesion kinase (FAK) plays an important role in vascular development, including the regulation of endothelial cell (EC) adhesion, migration, proliferation, and survival. 3'-deoxyadenosine (cordycepin) is known to suppress FAK expression, cell migration, and the epithelial?mesenchymal transition in hepatocellular carcinoma (HCC). However, whether cordycepin affects FAK expression and cellular functions in ECs and the specific molecular mechanism remain unclear. In this study, we found that cordycepin suppressed FAK expression and the phosphorylation of FAK (p-FAK) at Tyr397 in ECs. Cordycepin inhibited the proliferation, wound healing, transwell migration, and tube formation of ECs. Confocal microscopy revealed that cordycepin significantly reduced FAK expression and decreased focal adhesion number of ECs. The suppressed expression of FAK was accompanied by induced p53 and p21 expression in ECs. Finally, we demonstrated that cordycepin suppressed angiogenesis in an in vivo angiogenesis assay and reduced HCC tumor growth in a xenograft nude mice model. Our study indicated that cordycepin could attenuate cell proliferation and migration and may result in the impairment of the angiogenesis process and tumor growth via downregulation of FAK and induction of p53 and p21 in ECs. Therefore, cordycepin may be used as a potential adjuvant for cancer therapy.

SUBMITTER: Lin YT 

PROVIDER: S-EPMC6406613 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53.

Lin Yi-Ting YT   Liang Shu-Man SM   Wu Ya-Ju YJ   Wu Yi-Ju YJ   Lu Yi-Jhu YJ   Jan Yee-Jee YJ   Ko Bor-Sheng BS   Chuang Yung-Jen YJ   Shyue Song-Kun SK   Kuo Cheng-Chin CC   Liou Jun-Yang JY  

Cancers 20190201 2


Focal adhesion kinase (FAK) plays an important role in vascular development, including the regulation of endothelial cell (EC) adhesion, migration, proliferation, and survival. 3'-deoxyadenosine (cordycepin) is known to suppress FAK expression, cell migration, and the epithelial⁻mesenchymal transition in hepatocellular carcinoma (HCC). However, whether cordycepin affects FAK expression and cellular functions in ECs and the specific molecular mechanism remain unclear. In this study, we found that  ...[more]

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