title: Thrombomodulin mediates the migration of cervical cancer cells through the regulation of epithelial-mesenchymal transition biomarkers.
abstract: Thrombomodulin (TM) has been shown to regulate many physiological and pathological processes, including inflammation, thrombosis, and tumor progression. TM is also a natural anticoagulant that maintains circulatory homeostasis in endothelial cells. However, little is known regarding the role of TM in the progression and metastasis of cervical cancer. TM-specific RNA interference and a cDNA expression vector were used to manipulate TM expression in cervical cancer cells. Cell growth and cell migration were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, transwell migration assays, and a biosensor system. TM silencing did not affect the growth rate of the cells. However, cell migration was dramatically enhanced after silencing of TM in HeLa cells. The overexpression of TM in cervical cancer cells only slightly influenced their proliferative capacity. After overexpression of TM in HeLa cells, their migratory capability was suppressed. Furthermore, we found that the decreased expression of E-cadherin and increase of zeb-1 and snail expression in TM-silenced cells which may be correlated with the results of knocking-down TM increases the migratory ability in this study. Our results demonstrate that TM may slightly regulate the growth but played the important role in the migratory ability of cervical cancer cells, suggesting that TM could potentially serve as a novel prognostic and therapeutic target in cervical cancer.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Cheng-Jeng
authors.initials: CJ
authors.lastname: Tai
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Cheng
authors.forename: Hou-Yu
authors.initials: HY
authors.lastname: Su
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Wu
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
authors.forename: Chien-Kai
authors.initials: CK
authors.lastname: Wang
authors.forename: Chen-Jei
authors.initials: CJ
authors.lastname: Tai
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
mesh_terms: D015415:Biomarkers; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018180:Thrombomodulin / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D034741:RNA, Small Interfering; D018180:Thrombomodulin