title: Cordycepin suppresses integrin/FAK signaling and epithelial-mesenchymal transition in hepatocellular carcinoma.
abstract: Cordycepin, also known as 3-deoxyadenosine, is an analogue of adenosine extracted from the traditional Chinese medicine "Dong Chong Xia Cao". Cordycepin is an active small molecular weight compound and is implicated in modulating multiple physiological functions including immune activation, anti-aging and anti-tumor effects. Several studies have indicated that cordycepin suppresses tumor progression. However, the signaling pathways involved in cordycepin regulating cancer cell motility, invasiveness and epithelial-mesenchymal transition (EMT) remain unclear. In this study, we found that cordycepin inhibits hepatocellular carcinoma (HCC) cell proliferation and migration/invasion. Treatment of cordycepin results in the increasing expression of epithelial marker, Ecadherin while no significant effect was found on N-cadherin α-catenin and β-catenin. Furthermore, although the expression of focal adhesion kinase (FAK) was slightly reduced, the level of phosphorylated FAK was significantly reduced by the treatment of cordycepin. In addition, cordycepin significantly suppresses the expression of integrin α3, integrin α6 and integrin β1 which are crucial interacting partners of FAK in regulating the focal adhesion complex. These results suggest cordycepin may contribute to EMT, antimigration/ invasion and growth inhibitory effects of HCC by suppressing E-cadherin and integrin/FAK signaling. Thus, cordycepin is a potential therapeutic or supplementary agent for preventing HCC tumor progression.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Yao
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Tzu-An
authors.initials: TA
authors.lastname: Liu
authors.forename: Shu-Man
authors.initials: SM
authors.lastname: Liang
authors.forename: Chia-Chia
authors.initials: CC
authors.lastname: Liu
authors.forename: Yi-Jhu
authors.initials: YJ
authors.lastname: Lu
authors.forename: Shean-Shong
authors.initials: SS
authors.lastname: Tzean
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan. jliou@nhri.org.tw.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Liou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D039121:Integrin alpha6beta1 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D003839:Deoxyadenosines; D039201:Integrin alpha3beta1; D039121:Integrin alpha6beta1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C058120:cordycepin