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

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 transiti...

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Autores principales: Lin, Yi-Ting, Liang, Shu-Man, Wu, Ya-Ju, Wu, Yi-Ju, Lu, Yi-Jhu, Jan, Yee-Jee, Ko, Bor-Sheng, Chuang, Yung-Jen, Shyue, Song-Kun, Kuo, Cheng-Chin, Liou, Jun-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406613/
https://www.ncbi.nlm.nih.gov/pubmed/30717276
http://dx.doi.org/10.3390/cancers11020168
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author Lin, Yi-Ting
Liang, Shu-Man
Wu, Ya-Ju
Wu, Yi-Ju
Lu, Yi-Jhu
Jan, Yee-Jee
Ko, Bor-Sheng
Chuang, Yung-Jen
Shyue, Song-Kun
Kuo, Cheng-Chin
Liou, Jun-Yang
author_facet Lin, Yi-Ting
Liang, Shu-Man
Wu, Ya-Ju
Wu, Yi-Ju
Lu, Yi-Jhu
Jan, Yee-Jee
Ko, Bor-Sheng
Chuang, Yung-Jen
Shyue, Song-Kun
Kuo, Cheng-Chin
Liou, Jun-Yang
author_sort Lin, Yi-Ting
collection PubMed
description 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.
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spelling pubmed-64066132019-03-21 Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53 Lin, Yi-Ting Liang, Shu-Man Wu, Ya-Ju Wu, Yi-Ju Lu, Yi-Jhu Jan, Yee-Jee Ko, Bor-Sheng Chuang, Yung-Jen Shyue, Song-Kun Kuo, Cheng-Chin Liou, Jun-Yang Cancers (Basel) Article 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. MDPI 2019-02-01 /pmc/articles/PMC6406613/ /pubmed/30717276 http://dx.doi.org/10.3390/cancers11020168 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Yi-Ting
Liang, Shu-Man
Wu, Ya-Ju
Wu, Yi-Ju
Lu, Yi-Jhu
Jan, Yee-Jee
Ko, Bor-Sheng
Chuang, Yung-Jen
Shyue, Song-Kun
Kuo, Cheng-Chin
Liou, Jun-Yang
Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53
title Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53
title_full Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53
title_fullStr Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53
title_full_unstemmed Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53
title_short Cordycepin Suppresses Endothelial Cell Proliferation, Migration, Angiogenesis, and Tumor Growth by Regulating Focal Adhesion Kinase and p53
title_sort cordycepin suppresses endothelial cell proliferation, migration, angiogenesis, and tumor growth by regulating focal adhesion kinase and p53
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406613/
https://www.ncbi.nlm.nih.gov/pubmed/30717276
http://dx.doi.org/10.3390/cancers11020168
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